Insulin receptor substrate-1 involvement in epidermal growth factor receptor and insulin-like growth factor receptor signalling: implication for Gefitinib (‘Iressa’) response ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2008-09

AUTHORS

Janice M. Knowlden, Helen E. Jones, Denise Barrow, Julia M. W. Gee, Robert I. Nicholson, Iain R. Hutcheson

ABSTRACT

Classically the insulin receptor substrate-1 (IRS-1) is an essential component of insulin-like growth factor type 1 receptor (IGF-IR) signalling, providing an interface between the receptor and key downstream signalling cascades. Here, however, we show that in tamoxifen-resistant MCF-7 (Tam-R) breast cancer cells, that are highly dependent on epidermal growth factor receptor (EGFR) for growth, IRS-1 can interact with EGFR and be preferentially phosphorylated on tyrosine (Y) 896, a Grb2 binding site. Indeed, phosphorylation of this site is greatly enhanced by exposure of these cells, and other EGFR-positive cell lines, to EGF. Importantly, while IGF-II promotes phosphorylation of IRS-1 on Y612, a PI3-K recruitment site, it has limited effect on Y896 phosphorylation in Tam-R cells. Furthermore, EGF and IGF-II co-treatment, reduces the ability of IGF-II to phosphorylate Y612, whilst maintaining Y896 phosphorylation, suggesting that the EGFR is the dominant recruiter of IRS-1 in this cell line. Significantly, challenge of Tam-R cells with the EGFR-selective tyrosine kinase inhibitor gefitinib, for 7 days, reduces IRS-1/EGFR association and IRS-1 Y896 phosphorylation, while promoting IRS-1/IGF-IR association and IRS-1 Y612 phosphorylation. Furthermore, gefitinib significantly enhances IGF-II-mediated phosphorylation of IRS-1 Y612 and AKT in Tam-R cells. Importantly, induction of this pathway by gefitinib can be abrogated by inhibition/downregulation of the IGF-IR. Our data would therefore suggest a novel association exists between the EGFR and IRS-1 in several EGFR-positive cancer cell lines. This association acts to promote phosphorylation of IRS-1 at Y896 and drive MAPK signalling whilst preventing recruitment of IRS-1 by the IGF-IR and inhibiting signalling via this receptor. Treatment with gefitinib alters the dynamics of this system, promoting IGF-IR signalling, the dominant gefitinib-resistant growth regulatory pathway in Tam-R cells, thus, potentially limiting its efficacy. More... »

PAGES

79-91

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10549-007-9763-9

DOI

http://dx.doi.org/10.1007/s10549-007-9763-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1037907096

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17902048


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biochemistry and Cell Biology", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biological Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Adaptor Proteins, Signal Transducing", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Antineoplastic Agents", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Blotting, Western", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Breast Neoplasms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Line, Tumor", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Drug Resistance, Neoplasm", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "ErbB Receptors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Female", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Gefitinib", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Immunoprecipitation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Insulin Receptor Substrate Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Lung Neoplasms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Male", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Neoplasms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Prostatic Neoplasms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Quinazolines", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Receptor Cross-Talk", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Receptors, Somatomedin", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Signal Transduction", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Cardiff University", 
          "id": "https://www.grid.ac/institutes/grid.5600.3", 
          "name": [
            "Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, CF10 3XF, Cardiff, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Knowlden", 
        "givenName": "Janice M.", 
        "id": "sg:person.01211220110.63", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01211220110.63"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Cardiff University", 
          "id": "https://www.grid.ac/institutes/grid.5600.3", 
          "name": [
            "Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, CF10 3XF, Cardiff, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Jones", 
        "givenName": "Helen E.", 
        "id": "sg:person.01247003636.76", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01247003636.76"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Cardiff University", 
          "id": "https://www.grid.ac/institutes/grid.5600.3", 
          "name": [
            "Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, CF10 3XF, Cardiff, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Barrow", 
        "givenName": "Denise", 
        "id": "sg:person.01277511160.33", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01277511160.33"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Cardiff University", 
          "id": "https://www.grid.ac/institutes/grid.5600.3", 
          "name": [
            "Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, CF10 3XF, Cardiff, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gee", 
        "givenName": "Julia M. W.", 
        "id": "sg:person.012457220672.07", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012457220672.07"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Cardiff University", 
          "id": "https://www.grid.ac/institutes/grid.5600.3", 
          "name": [
            "Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, CF10 3XF, Cardiff, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Nicholson", 
        "givenName": "Robert I.", 
        "id": "sg:person.0670333460.58", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0670333460.58"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Cardiff University", 
          "id": "https://www.grid.ac/institutes/grid.5600.3", 
          "name": [
            "Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, CF10 3XF, Cardiff, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Hutcheson", 
        "givenName": "Iain R.", 
        "id": "sg:person.01143104710.88", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01143104710.88"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/sj.bjc.6601921", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000414058", 
          "https://doi.org/10.1038/sj.bjc.6601921"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.bjc.6601921", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000414058", 
          "https://doi.org/10.1038/sj.bjc.6601921"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1206388", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004564925", 
          "https://doi.org/10.1038/sj.onc.1206388"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1206388", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004564925", 
          "https://doi.org/10.1038/sj.onc.1206388"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1046/j.1432-1327.2001.02327.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008167468"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m000412200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009241429"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1046/j.1432-1327.2001.01831.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011629817"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0959-8049(01)00231-3", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011723495"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1023/b:brea.0000041623.21338.47", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015249151", 
          "https://doi.org/10.1023/b:brea.0000041623.21338.47"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1677/erc.1.00799", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015606139"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1677/erc.1.00799", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015606139"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/bcr1028", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018289267", 
          "https://doi.org/10.1186/bcr1028"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1634/theoncologist.7-suppl_4-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019857496"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/jnci/93.24.1852", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022747550"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/1040-8428(94)00144-i", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027064147"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1677/erc.1.00992", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028888523"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s001250051387", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029374185", 
          "https://doi.org/10.1007/s001250051387"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s001250051387", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029374185", 
          "https://doi.org/10.1007/s001250051387"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature04177", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033468470", 
          "https://doi.org/10.1038/nature04177"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature04177", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033468470", 
          "https://doi.org/10.1038/nature04177"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature04177", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033468470", 
          "https://doi.org/10.1038/nature04177"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1099314", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033538744"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1210/en.2002-220620", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033760962"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1204277", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034076763", 
          "https://doi.org/10.1038/sj.onc.1204277"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1204277", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034076763", 
          "https://doi.org/10.1038/sj.onc.1204277"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1677/erc.1.01059", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034112291"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1053/sonc.2002.31521", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037819249"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1042/bj20020903", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038309123"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1042/bj20020903", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038309123"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/ijc.11445", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039084964"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2005.11.890", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040419394"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/emboj/19.13.3159", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040473291"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.270.25.14863", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042170678"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmoa040938", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042907590"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2217/14796694.1.4.461", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043722359"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1203587", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045386828", 
          "https://doi.org/10.1038/sj.onc.1203587"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1203587", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045386828", 
          "https://doi.org/10.1038/sj.onc.1203587"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.bjc.6603237", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049475665", 
          "https://doi.org/10.1038/sj.bjc.6603237"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.bjc.6603237", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049475665", 
          "https://doi.org/10.1038/sj.bjc.6603237"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/jnci/85.16.1327", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1059818100"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-031206", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1063224756"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2002.10.112", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1064203155"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1064245480", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1210/en.2005-0247", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1064247375"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1210/endo.136.2.7835273", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1064279945"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1210/endo.142.7.8283", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1064284476"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1517/14796694.1.2.221", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1067590514"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1517/14796694.1.2.221", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1067590514"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1074976743", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/j.1460-2075.1986.tb04528.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1079436431"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1083124264", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1083346988", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2008-09", 
    "datePublishedReg": "2008-09-01", 
    "description": "Classically the insulin receptor substrate-1 (IRS-1) is an essential component of insulin-like growth factor type 1 receptor (IGF-IR) signalling, providing an interface between the receptor and key downstream signalling cascades. Here, however, we show that in tamoxifen-resistant MCF-7 (Tam-R) breast cancer cells, that are highly dependent on epidermal growth factor receptor (EGFR) for growth, IRS-1 can interact with EGFR and be preferentially phosphorylated on tyrosine (Y) 896, a Grb2 binding site. Indeed, phosphorylation of this site is greatly enhanced by exposure of these cells, and other EGFR-positive cell lines, to EGF. Importantly, while IGF-II promotes phosphorylation of IRS-1 on Y612, a PI3-K recruitment site, it has limited effect on Y896 phosphorylation in Tam-R cells. Furthermore, EGF and IGF-II co-treatment, reduces the ability of IGF-II to phosphorylate Y612, whilst maintaining Y896 phosphorylation, suggesting that the EGFR is the dominant recruiter of IRS-1 in this cell line. Significantly, challenge of Tam-R cells with the EGFR-selective tyrosine kinase inhibitor gefitinib, for 7 days, reduces IRS-1/EGFR association and IRS-1 Y896 phosphorylation, while promoting IRS-1/IGF-IR association and IRS-1 Y612 phosphorylation. Furthermore, gefitinib significantly enhances IGF-II-mediated phosphorylation of IRS-1 Y612 and AKT in Tam-R cells. Importantly, induction of this pathway by gefitinib can be abrogated by inhibition/downregulation of the IGF-IR. Our data would therefore suggest a novel association exists between the EGFR and IRS-1 in several EGFR-positive cancer cell lines. This association acts to promote phosphorylation of IRS-1 at Y896 and drive MAPK signalling whilst preventing recruitment of IRS-1 by the IGF-IR and inhibiting signalling via this receptor. Treatment with gefitinib alters the dynamics of this system, promoting IGF-IR signalling, the dominant gefitinib-resistant growth regulatory pathway in Tam-R cells, thus, potentially limiting its efficacy.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1007/s10549-007-9763-9", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": false, 
    "isPartOf": [
      {
        "id": "sg:journal.1092777", 
        "issn": [
          "0167-6806", 
          "1573-7217"
        ], 
        "name": "Breast Cancer Research and Treatment", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "111"
      }
    ], 
    "name": "Insulin receptor substrate-1 involvement in epidermal growth factor receptor and insulin-like growth factor receptor signalling: implication for Gefitinib (\u2018Iressa\u2019) response and resistance", 
    "pagination": "79-91", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "b4938c5dd138362866ba2deb74e0ae8b2b1ba404c4c846a0ad712bbed267b9c1"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "17902048"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "8111104"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1007/s10549-007-9763-9"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1037907096"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1007/s10549-007-9763-9", 
      "https://app.dimensions.ai/details/publication/pub.1037907096"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T14:31", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000373_0000000373/records_13096_00000001.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "http://link.springer.com/10.1007/s10549-007-9763-9"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s10549-007-9763-9'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s10549-007-9763-9'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s10549-007-9763-9'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s10549-007-9763-9'


 

This table displays all metadata directly associated to this object as RDF triples.

312 TRIPLES      21 PREDICATES      90 URIs      41 LITERALS      29 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1007/s10549-007-9763-9 schema:about N0219a02edeec452b816f77f4a00fb9ba
2 N20e1c6bd6cf448a1bc6206155963a42b
3 N279ea3f0a34e458cb7e0fa97b221c5da
4 N308e3264d35040f08f2e0d9194683ede
5 N47c2b9ac38a248158505d3c62e145c0e
6 N48056cffc3314bb68a45fb69553a288a
7 N480e488fc9fd4283836861b02187e030
8 N4dfd1a2d148b42139b5a820349b11e72
9 N7111c5261ae8413d9a0207f582151886
10 N7b1d244c7f5e49eab80b89ec1e5e5fc7
11 N7fe26018d2104a27bfc8031e650fd686
12 N83490feddad04791afe5df4a5f8deeab
13 Na295b4c3863248cc84c14b93113cfe7c
14 Na2ccf7d5cb9744feb754484fe91a8d1c
15 Nb56396c72d744340af60ed044fa581f6
16 Nb6fc04d066024fd2af57231868d9d2d6
17 Ncc5cbf574fcf4a67843914604f984903
18 Ndaaff3815bdf4a98837466504a5a046e
19 Nf9581252edce44e9afd2192a0fdede1a
20 Nfb81ed9884664ccaae8e1964b2ae94ee
21 anzsrc-for:06
22 anzsrc-for:0601
23 schema:author N134a7a9c26f3496e841e71270e0bca5f
24 schema:citation sg:pub.10.1007/s001250051387
25 sg:pub.10.1023/b:brea.0000041623.21338.47
26 sg:pub.10.1038/nature04177
27 sg:pub.10.1038/sj.bjc.6601921
28 sg:pub.10.1038/sj.bjc.6603237
29 sg:pub.10.1038/sj.onc.1203587
30 sg:pub.10.1038/sj.onc.1204277
31 sg:pub.10.1038/sj.onc.1206388
32 sg:pub.10.1186/bcr1028
33 https://app.dimensions.ai/details/publication/pub.1064245480
34 https://app.dimensions.ai/details/publication/pub.1074976743
35 https://app.dimensions.ai/details/publication/pub.1083124264
36 https://app.dimensions.ai/details/publication/pub.1083346988
37 https://doi.org/10.1002/ijc.11445
38 https://doi.org/10.1002/j.1460-2075.1986.tb04528.x
39 https://doi.org/10.1016/1040-8428(94)00144-i
40 https://doi.org/10.1016/s0959-8049(01)00231-3
41 https://doi.org/10.1042/bj20020903
42 https://doi.org/10.1046/j.1432-1327.2001.01831.x
43 https://doi.org/10.1046/j.1432-1327.2001.02327.x
44 https://doi.org/10.1053/sonc.2002.31521
45 https://doi.org/10.1056/nejmoa040938
46 https://doi.org/10.1074/jbc.270.25.14863
47 https://doi.org/10.1074/jbc.m000412200
48 https://doi.org/10.1093/emboj/19.13.3159
49 https://doi.org/10.1093/jnci/85.16.1327
50 https://doi.org/10.1093/jnci/93.24.1852
51 https://doi.org/10.1126/science.1099314
52 https://doi.org/10.1158/1078-0432.ccr-031206
53 https://doi.org/10.1200/jco.2002.10.112
54 https://doi.org/10.1200/jco.2005.11.890
55 https://doi.org/10.1210/en.2002-220620
56 https://doi.org/10.1210/en.2005-0247
57 https://doi.org/10.1210/endo.136.2.7835273
58 https://doi.org/10.1210/endo.142.7.8283
59 https://doi.org/10.1517/14796694.1.2.221
60 https://doi.org/10.1634/theoncologist.7-suppl_4-2
61 https://doi.org/10.1677/erc.1.00799
62 https://doi.org/10.1677/erc.1.00992
63 https://doi.org/10.1677/erc.1.01059
64 https://doi.org/10.2217/14796694.1.4.461
65 schema:datePublished 2008-09
66 schema:datePublishedReg 2008-09-01
67 schema:description Classically the insulin receptor substrate-1 (IRS-1) is an essential component of insulin-like growth factor type 1 receptor (IGF-IR) signalling, providing an interface between the receptor and key downstream signalling cascades. Here, however, we show that in tamoxifen-resistant MCF-7 (Tam-R) breast cancer cells, that are highly dependent on epidermal growth factor receptor (EGFR) for growth, IRS-1 can interact with EGFR and be preferentially phosphorylated on tyrosine (Y) 896, a Grb2 binding site. Indeed, phosphorylation of this site is greatly enhanced by exposure of these cells, and other EGFR-positive cell lines, to EGF. Importantly, while IGF-II promotes phosphorylation of IRS-1 on Y612, a PI3-K recruitment site, it has limited effect on Y896 phosphorylation in Tam-R cells. Furthermore, EGF and IGF-II co-treatment, reduces the ability of IGF-II to phosphorylate Y612, whilst maintaining Y896 phosphorylation, suggesting that the EGFR is the dominant recruiter of IRS-1 in this cell line. Significantly, challenge of Tam-R cells with the EGFR-selective tyrosine kinase inhibitor gefitinib, for 7 days, reduces IRS-1/EGFR association and IRS-1 Y896 phosphorylation, while promoting IRS-1/IGF-IR association and IRS-1 Y612 phosphorylation. Furthermore, gefitinib significantly enhances IGF-II-mediated phosphorylation of IRS-1 Y612 and AKT in Tam-R cells. Importantly, induction of this pathway by gefitinib can be abrogated by inhibition/downregulation of the IGF-IR. Our data would therefore suggest a novel association exists between the EGFR and IRS-1 in several EGFR-positive cancer cell lines. This association acts to promote phosphorylation of IRS-1 at Y896 and drive MAPK signalling whilst preventing recruitment of IRS-1 by the IGF-IR and inhibiting signalling via this receptor. Treatment with gefitinib alters the dynamics of this system, promoting IGF-IR signalling, the dominant gefitinib-resistant growth regulatory pathway in Tam-R cells, thus, potentially limiting its efficacy.
68 schema:genre research_article
69 schema:inLanguage en
70 schema:isAccessibleForFree false
71 schema:isPartOf N4a23cd619cc740cfb637bd083d9bab5b
72 Nf726c31e90e344b6a46ca2224abf2b4e
73 sg:journal.1092777
74 schema:name Insulin receptor substrate-1 involvement in epidermal growth factor receptor and insulin-like growth factor receptor signalling: implication for Gefitinib (‘Iressa’) response and resistance
75 schema:pagination 79-91
76 schema:productId N01628ce3686a45baacb65ebb97ceb148
77 N455355e8fd8c4338a73912dbc21b528c
78 Na037db54a5994c78a201bf96d466d49c
79 Na8df7698af154904b3a7a837e9464c7b
80 Ne529a60aa06d499085334f81dc8dc6cc
81 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037907096
82 https://doi.org/10.1007/s10549-007-9763-9
83 schema:sdDatePublished 2019-04-11T14:31
84 schema:sdLicense https://scigraph.springernature.com/explorer/license/
85 schema:sdPublisher N7fe100023dfa431ea035be6e9f089d0d
86 schema:url http://link.springer.com/10.1007/s10549-007-9763-9
87 sgo:license sg:explorer/license/
88 sgo:sdDataset articles
89 rdf:type schema:ScholarlyArticle
90 N01628ce3686a45baacb65ebb97ceb148 schema:name doi
91 schema:value 10.1007/s10549-007-9763-9
92 rdf:type schema:PropertyValue
93 N0219a02edeec452b816f77f4a00fb9ba schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
94 schema:name Breast Neoplasms
95 rdf:type schema:DefinedTerm
96 N134a7a9c26f3496e841e71270e0bca5f rdf:first sg:person.01211220110.63
97 rdf:rest N1a76796ab62d4700b507f56237bedcc9
98 N1a76796ab62d4700b507f56237bedcc9 rdf:first sg:person.01247003636.76
99 rdf:rest Nbbb32b42737a4ffd935fb5239fa429ff
100 N20e1c6bd6cf448a1bc6206155963a42b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
101 schema:name Gefitinib
102 rdf:type schema:DefinedTerm
103 N279ea3f0a34e458cb7e0fa97b221c5da schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
104 schema:name Quinazolines
105 rdf:type schema:DefinedTerm
106 N308e3264d35040f08f2e0d9194683ede schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
107 schema:name Blotting, Western
108 rdf:type schema:DefinedTerm
109 N455355e8fd8c4338a73912dbc21b528c schema:name readcube_id
110 schema:value b4938c5dd138362866ba2deb74e0ae8b2b1ba404c4c846a0ad712bbed267b9c1
111 rdf:type schema:PropertyValue
112 N47c2b9ac38a248158505d3c62e145c0e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
113 schema:name Lung Neoplasms
114 rdf:type schema:DefinedTerm
115 N48056cffc3314bb68a45fb69553a288a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
116 schema:name Humans
117 rdf:type schema:DefinedTerm
118 N480e488fc9fd4283836861b02187e030 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
119 schema:name Cell Line, Tumor
120 rdf:type schema:DefinedTerm
121 N4a23cd619cc740cfb637bd083d9bab5b schema:issueNumber 1
122 rdf:type schema:PublicationIssue
123 N4dfd1a2d148b42139b5a820349b11e72 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
124 schema:name Antineoplastic Agents
125 rdf:type schema:DefinedTerm
126 N65fb2aa667c04601a81d9559863966d3 rdf:first sg:person.012457220672.07
127 rdf:rest Nfac68f72eda9439ab950e1e672c2dfec
128 N7111c5261ae8413d9a0207f582151886 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
129 schema:name Signal Transduction
130 rdf:type schema:DefinedTerm
131 N7b1d244c7f5e49eab80b89ec1e5e5fc7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
132 schema:name Male
133 rdf:type schema:DefinedTerm
134 N7fe100023dfa431ea035be6e9f089d0d schema:name Springer Nature - SN SciGraph project
135 rdf:type schema:Organization
136 N7fe26018d2104a27bfc8031e650fd686 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
137 schema:name Neoplasms
138 rdf:type schema:DefinedTerm
139 N83490feddad04791afe5df4a5f8deeab schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
140 schema:name Receptors, Somatomedin
141 rdf:type schema:DefinedTerm
142 Na037db54a5994c78a201bf96d466d49c schema:name dimensions_id
143 schema:value pub.1037907096
144 rdf:type schema:PropertyValue
145 Na295b4c3863248cc84c14b93113cfe7c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
146 schema:name Insulin Receptor Substrate Proteins
147 rdf:type schema:DefinedTerm
148 Na2ccf7d5cb9744feb754484fe91a8d1c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
149 schema:name Prostatic Neoplasms
150 rdf:type schema:DefinedTerm
151 Na8df7698af154904b3a7a837e9464c7b schema:name nlm_unique_id
152 schema:value 8111104
153 rdf:type schema:PropertyValue
154 Nb56396c72d744340af60ed044fa581f6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
155 schema:name ErbB Receptors
156 rdf:type schema:DefinedTerm
157 Nb6fc04d066024fd2af57231868d9d2d6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
158 schema:name Adaptor Proteins, Signal Transducing
159 rdf:type schema:DefinedTerm
160 Nbbb32b42737a4ffd935fb5239fa429ff rdf:first sg:person.01277511160.33
161 rdf:rest N65fb2aa667c04601a81d9559863966d3
162 Ncc5cbf574fcf4a67843914604f984903 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
163 schema:name Receptor Cross-Talk
164 rdf:type schema:DefinedTerm
165 Nd236e27fb52940fab7ae76f77d96bf20 rdf:first sg:person.01143104710.88
166 rdf:rest rdf:nil
167 Ndaaff3815bdf4a98837466504a5a046e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
168 schema:name Drug Resistance, Neoplasm
169 rdf:type schema:DefinedTerm
170 Ne529a60aa06d499085334f81dc8dc6cc schema:name pubmed_id
171 schema:value 17902048
172 rdf:type schema:PropertyValue
173 Nf726c31e90e344b6a46ca2224abf2b4e schema:volumeNumber 111
174 rdf:type schema:PublicationVolume
175 Nf9581252edce44e9afd2192a0fdede1a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
176 schema:name Immunoprecipitation
177 rdf:type schema:DefinedTerm
178 Nfac68f72eda9439ab950e1e672c2dfec rdf:first sg:person.0670333460.58
179 rdf:rest Nd236e27fb52940fab7ae76f77d96bf20
180 Nfb81ed9884664ccaae8e1964b2ae94ee schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
181 schema:name Female
182 rdf:type schema:DefinedTerm
183 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
184 schema:name Biological Sciences
185 rdf:type schema:DefinedTerm
186 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
187 schema:name Biochemistry and Cell Biology
188 rdf:type schema:DefinedTerm
189 sg:journal.1092777 schema:issn 0167-6806
190 1573-7217
191 schema:name Breast Cancer Research and Treatment
192 rdf:type schema:Periodical
193 sg:person.01143104710.88 schema:affiliation https://www.grid.ac/institutes/grid.5600.3
194 schema:familyName Hutcheson
195 schema:givenName Iain R.
196 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01143104710.88
197 rdf:type schema:Person
198 sg:person.01211220110.63 schema:affiliation https://www.grid.ac/institutes/grid.5600.3
199 schema:familyName Knowlden
200 schema:givenName Janice M.
201 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01211220110.63
202 rdf:type schema:Person
203 sg:person.012457220672.07 schema:affiliation https://www.grid.ac/institutes/grid.5600.3
204 schema:familyName Gee
205 schema:givenName Julia M. W.
206 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012457220672.07
207 rdf:type schema:Person
208 sg:person.01247003636.76 schema:affiliation https://www.grid.ac/institutes/grid.5600.3
209 schema:familyName Jones
210 schema:givenName Helen E.
211 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01247003636.76
212 rdf:type schema:Person
213 sg:person.01277511160.33 schema:affiliation https://www.grid.ac/institutes/grid.5600.3
214 schema:familyName Barrow
215 schema:givenName Denise
216 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01277511160.33
217 rdf:type schema:Person
218 sg:person.0670333460.58 schema:affiliation https://www.grid.ac/institutes/grid.5600.3
219 schema:familyName Nicholson
220 schema:givenName Robert I.
221 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0670333460.58
222 rdf:type schema:Person
223 sg:pub.10.1007/s001250051387 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029374185
224 https://doi.org/10.1007/s001250051387
225 rdf:type schema:CreativeWork
226 sg:pub.10.1023/b:brea.0000041623.21338.47 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015249151
227 https://doi.org/10.1023/b:brea.0000041623.21338.47
228 rdf:type schema:CreativeWork
229 sg:pub.10.1038/nature04177 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033468470
230 https://doi.org/10.1038/nature04177
231 rdf:type schema:CreativeWork
232 sg:pub.10.1038/sj.bjc.6601921 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000414058
233 https://doi.org/10.1038/sj.bjc.6601921
234 rdf:type schema:CreativeWork
235 sg:pub.10.1038/sj.bjc.6603237 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049475665
236 https://doi.org/10.1038/sj.bjc.6603237
237 rdf:type schema:CreativeWork
238 sg:pub.10.1038/sj.onc.1203587 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045386828
239 https://doi.org/10.1038/sj.onc.1203587
240 rdf:type schema:CreativeWork
241 sg:pub.10.1038/sj.onc.1204277 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034076763
242 https://doi.org/10.1038/sj.onc.1204277
243 rdf:type schema:CreativeWork
244 sg:pub.10.1038/sj.onc.1206388 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004564925
245 https://doi.org/10.1038/sj.onc.1206388
246 rdf:type schema:CreativeWork
247 sg:pub.10.1186/bcr1028 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018289267
248 https://doi.org/10.1186/bcr1028
249 rdf:type schema:CreativeWork
250 https://app.dimensions.ai/details/publication/pub.1064245480 schema:CreativeWork
251 https://app.dimensions.ai/details/publication/pub.1074976743 schema:CreativeWork
252 https://app.dimensions.ai/details/publication/pub.1083124264 schema:CreativeWork
253 https://app.dimensions.ai/details/publication/pub.1083346988 schema:CreativeWork
254 https://doi.org/10.1002/ijc.11445 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039084964
255 rdf:type schema:CreativeWork
256 https://doi.org/10.1002/j.1460-2075.1986.tb04528.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1079436431
257 rdf:type schema:CreativeWork
258 https://doi.org/10.1016/1040-8428(94)00144-i schema:sameAs https://app.dimensions.ai/details/publication/pub.1027064147
259 rdf:type schema:CreativeWork
260 https://doi.org/10.1016/s0959-8049(01)00231-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011723495
261 rdf:type schema:CreativeWork
262 https://doi.org/10.1042/bj20020903 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038309123
263 rdf:type schema:CreativeWork
264 https://doi.org/10.1046/j.1432-1327.2001.01831.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1011629817
265 rdf:type schema:CreativeWork
266 https://doi.org/10.1046/j.1432-1327.2001.02327.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1008167468
267 rdf:type schema:CreativeWork
268 https://doi.org/10.1053/sonc.2002.31521 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037819249
269 rdf:type schema:CreativeWork
270 https://doi.org/10.1056/nejmoa040938 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042907590
271 rdf:type schema:CreativeWork
272 https://doi.org/10.1074/jbc.270.25.14863 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042170678
273 rdf:type schema:CreativeWork
274 https://doi.org/10.1074/jbc.m000412200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009241429
275 rdf:type schema:CreativeWork
276 https://doi.org/10.1093/emboj/19.13.3159 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040473291
277 rdf:type schema:CreativeWork
278 https://doi.org/10.1093/jnci/85.16.1327 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059818100
279 rdf:type schema:CreativeWork
280 https://doi.org/10.1093/jnci/93.24.1852 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022747550
281 rdf:type schema:CreativeWork
282 https://doi.org/10.1126/science.1099314 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033538744
283 rdf:type schema:CreativeWork
284 https://doi.org/10.1158/1078-0432.ccr-031206 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063224756
285 rdf:type schema:CreativeWork
286 https://doi.org/10.1200/jco.2002.10.112 schema:sameAs https://app.dimensions.ai/details/publication/pub.1064203155
287 rdf:type schema:CreativeWork
288 https://doi.org/10.1200/jco.2005.11.890 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040419394
289 rdf:type schema:CreativeWork
290 https://doi.org/10.1210/en.2002-220620 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033760962
291 rdf:type schema:CreativeWork
292 https://doi.org/10.1210/en.2005-0247 schema:sameAs https://app.dimensions.ai/details/publication/pub.1064247375
293 rdf:type schema:CreativeWork
294 https://doi.org/10.1210/endo.136.2.7835273 schema:sameAs https://app.dimensions.ai/details/publication/pub.1064279945
295 rdf:type schema:CreativeWork
296 https://doi.org/10.1210/endo.142.7.8283 schema:sameAs https://app.dimensions.ai/details/publication/pub.1064284476
297 rdf:type schema:CreativeWork
298 https://doi.org/10.1517/14796694.1.2.221 schema:sameAs https://app.dimensions.ai/details/publication/pub.1067590514
299 rdf:type schema:CreativeWork
300 https://doi.org/10.1634/theoncologist.7-suppl_4-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019857496
301 rdf:type schema:CreativeWork
302 https://doi.org/10.1677/erc.1.00799 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015606139
303 rdf:type schema:CreativeWork
304 https://doi.org/10.1677/erc.1.00992 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028888523
305 rdf:type schema:CreativeWork
306 https://doi.org/10.1677/erc.1.01059 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034112291
307 rdf:type schema:CreativeWork
308 https://doi.org/10.2217/14796694.1.4.461 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043722359
309 rdf:type schema:CreativeWork
310 https://www.grid.ac/institutes/grid.5600.3 schema:alternateName Cardiff University
311 schema:name Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, CF10 3XF, Cardiff, UK
312 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...