Glycogen synthase kinase-3: a new therapeutic target in renal cell carcinoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-11-17

AUTHORS

V Bilim, A Ougolkov, K Yuuki, S Naito, H Kawazoe, A Muto, M Oya, D Billadeau, T Motoyama, Y Tomita

ABSTRACT

Background:Renal cell carcinoma (RCC) is highly resistant to chemotherapy because of a high apoptotic threshold. Recent evidences suggest that GSK-3β positively regulates human pancreatic cancer and leukaemia cell survival in part through regulation of nuclear factor (NF-κB)-mediated expression of anti-apoptotic molecules. Our objectives were to determine the expression pattern of GSK-3β and to assess the anti-cancer effect of GSK-3β inhibition in RCC.Methods:Immunohistochemistry and nuclear/cytosolic fractionation were performed to determine the expression pattern of GSK-3β in human RCCs. We used small molecule inhibitor, RNA interference, western blotting, quantitative RT–PCR, BrDU incorporation and MTS assays to study the effect of GSK-3β inactivation on renal cancer cell proliferation and survival.Results:We detected aberrant nuclear accumulation of GSK-3β in RCC cell lines and in 68 out of 74 (91.89%) human RCCs. We found that pharmacological inhibition of GSK-3 led to a decrease in proliferation and survival of renal cancer cells. We observed that inhibition of GSK-3 results in decreased expression of NF-κB target genes Bcl-2 and XIAP and a subsequent increase in renal cancer cell apoptosis. Moreover, we show that GSK-3 inhibitor and Docetaxel synergistically suppress proliferation and survival of renal cancer cells.Conclusions:Our results show nuclear accumulation of GSK-3β as a new marker of human RCC, identify that GSK-3 positively regulates RCC cell survival and proliferation and suggest inhibition of GSK-3 as a new promising approach in the treatment of human renal cancer. More... »

PAGES

2005-2014

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.bjc.6605437

DOI

http://dx.doi.org/10.1038/sj.bjc.6605437

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1016108440

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19920820


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/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Oncology and Carcinogenesis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Adult", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Aged", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Carcinoma, Renal Cell", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Proliferation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Survival", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Docetaxel", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Female", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Glycogen Synthase Kinase 3", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Glycogen Synthase Kinase 3 beta", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Kidney Neoplasms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Male", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Middle Aged", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "NF-kappa B", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Proto-Oncogene Proteins c-bcl-2", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Taxoids", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Thiazoles", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Urea", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "X-Linked Inhibitor of Apoptosis Protein", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Department of Urology, Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-9585, Yamagata, Japan", 
          "id": "http://www.grid.ac/institutes/grid.268394.2", 
          "name": [
            "Department of Urology, Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-9585, Yamagata, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Bilim", 
        "givenName": "V", 
        "id": "sg:person.01217564427.06", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01217564427.06"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Pathology, Feinberg School of Medicine, Northwestern University, Ward Building 3-140, 303 E. Chicago Avenue, 60611, Chicago, IL, USA", 
          "id": "http://www.grid.ac/institutes/grid.16753.36", 
          "name": [
            "Department of Pathology, Feinberg School of Medicine, Northwestern University, Ward Building 3-140, 303 E. Chicago Avenue, 60611, Chicago, IL, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ougolkov", 
        "givenName": "A", 
        "id": "sg:person.01176130410.78", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01176130410.78"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Urology, Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-9585, Yamagata, Japan", 
          "id": "http://www.grid.ac/institutes/grid.268394.2", 
          "name": [
            "Department of Urology, Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-9585, Yamagata, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Yuuki", 
        "givenName": "K", 
        "id": "sg:person.01077635223.15", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01077635223.15"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Urology, Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-9585, Yamagata, Japan", 
          "id": "http://www.grid.ac/institutes/grid.268394.2", 
          "name": [
            "Department of Urology, Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-9585, Yamagata, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Naito", 
        "givenName": "S", 
        "id": "sg:person.01214063623.55", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01214063623.55"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Urology, Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-9585, Yamagata, Japan", 
          "id": "http://www.grid.ac/institutes/grid.268394.2", 
          "name": [
            "Department of Urology, Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-9585, Yamagata, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kawazoe", 
        "givenName": "H", 
        "id": "sg:person.01066211163.29", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01066211163.29"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Urology, Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-9585, Yamagata, Japan", 
          "id": "http://www.grid.ac/institutes/grid.268394.2", 
          "name": [
            "Department of Urology, Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-9585, Yamagata, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Muto", 
        "givenName": "A", 
        "id": "sg:person.0717052177.19", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0717052177.19"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Urology, Keio University School of Medicine, Shinano-machi 35, Shinjuku-ku, Tokyo, Japan", 
          "id": "http://www.grid.ac/institutes/grid.26091.3c", 
          "name": [
            "Department of Urology, Keio University School of Medicine, Shinano-machi 35, Shinjuku-ku, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Oya", 
        "givenName": "M", 
        "id": "sg:person.01167102574.39", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01167102574.39"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Division of Oncology Research, Mayo Clinic College of Medicine, 200 First Street Southwest, 55905, Rochester, MN, USA", 
          "id": "http://www.grid.ac/institutes/grid.66875.3a", 
          "name": [
            "Division of Oncology Research, Mayo Clinic College of Medicine, 200 First Street Southwest, 55905, Rochester, MN, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Billadeau", 
        "givenName": "D", 
        "id": "sg:person.01106206356.85", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01106206356.85"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Human Pathology (Second Department of Pathology), Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-9585, Yamagata, Japan", 
          "id": "http://www.grid.ac/institutes/grid.268394.2", 
          "name": [
            "Department of Human Pathology (Second Department of Pathology), Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-9585, Yamagata, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Motoyama", 
        "givenName": "T", 
        "id": "sg:person.0712650615.38", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0712650615.38"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Urology, Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-9585, Yamagata, Japan", 
          "id": "http://www.grid.ac/institutes/grid.268394.2", 
          "name": [
            "Department of Urology, Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-9585, Yamagata, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Tomita", 
        "givenName": "Y", 
        "id": "sg:person.0610107330.58", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0610107330.58"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/sj.bjc.6604268", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033421639", 
          "https://doi.org/10.1038/sj.bjc.6604268"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.cr.7310078", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034472744", 
          "https://doi.org/10.1038/sj.cr.7310078"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/35017574", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044051571", 
          "https://doi.org/10.1038/35017574"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature07284", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026377853", 
          "https://doi.org/10.1038/nature07284"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1208068", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038643342", 
          "https://doi.org/10.1038/sj.onc.1208068"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1204525", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033274710", 
          "https://doi.org/10.1038/sj.onc.1204525"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1209346", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037518369", 
          "https://doi.org/10.1038/sj.onc.1209346"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.bjc.6603359", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005704871", 
          "https://doi.org/10.1038/sj.bjc.6603359"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/bf02524349", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010667071", 
          "https://doi.org/10.1007/bf02524349"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2009-11-17", 
    "datePublishedReg": "2009-11-17", 
    "description": "Background:Renal cell carcinoma (RCC) is highly resistant to chemotherapy because of a high apoptotic threshold. Recent evidences suggest that GSK-3\u03b2 positively regulates human pancreatic cancer and leukaemia cell survival in part through regulation of nuclear factor (NF-\u03baB)-mediated expression of anti-apoptotic molecules. Our objectives were to determine the expression pattern of GSK-3\u03b2 and to assess the anti-cancer effect of GSK-3\u03b2 inhibition in RCC.Methods:Immunohistochemistry and nuclear/cytosolic fractionation were performed to determine the expression pattern of GSK-3\u03b2 in human RCCs. We used small molecule inhibitor, RNA interference, western blotting, quantitative RT\u2013PCR, BrDU incorporation and MTS assays to study the effect of GSK-3\u03b2 inactivation on renal cancer cell proliferation and survival.Results:We detected aberrant nuclear accumulation of GSK-3\u03b2 in RCC cell lines and in 68 out of 74 (91.89%) human RCCs. We found that pharmacological inhibition of GSK-3 led to a decrease in proliferation and survival of renal cancer cells. We observed that inhibition of GSK-3 results in decreased expression of NF-\u03baB target genes Bcl-2 and XIAP and a subsequent increase in renal cancer cell apoptosis. Moreover, we show that GSK-3 inhibitor and Docetaxel synergistically suppress proliferation and survival of renal cancer cells.Conclusions:Our results show nuclear accumulation of GSK-3\u03b2 as a new marker of human RCC, identify that GSK-3 positively regulates RCC cell survival and proliferation and suggest inhibition of GSK-3 as a new promising approach in the treatment of human renal cancer.", 
    "genre": "article", 
    "id": "sg:pub.10.1038/sj.bjc.6605437", 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1017082", 
        "issn": [
          "0007-0920", 
          "1532-1827"
        ], 
        "name": "British Journal of Cancer", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "12", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "101"
      }
    ], 
    "keywords": [
      "renal cell carcinoma", 
      "human renal cell carcinoma", 
      "renal cancer cells", 
      "GSK-3\u03b2", 
      "cell carcinoma", 
      "renal cancer cell apoptosis", 
      "renal cancer cell proliferation", 
      "cancer cells", 
      "human pancreatic cancer", 
      "RCC cell survival", 
      "new therapeutic targets", 
      "anti-cancer effects", 
      "cancer cell proliferation", 
      "GSK-3", 
      "GSK-3\u03b2 inhibition", 
      "human renal cancer", 
      "RCC cell lines", 
      "cell survival", 
      "leukemia cell survival", 
      "aberrant nuclear accumulation", 
      "GSK-3\u03b2 inactivation", 
      "quantitative RT-PCR", 
      "high apoptotic threshold", 
      "anti-apoptotic molecules", 
      "cancer cell apoptosis", 
      "pancreatic cancer", 
      "renal cancer", 
      "target genes Bcl-2", 
      "therapeutic target", 
      "small molecule inhibitors", 
      "nuclear accumulation", 
      "GSK-3 results", 
      "suppress proliferation", 
      "gene Bcl-2", 
      "pharmacological inhibition", 
      "decreased expression", 
      "nuclear factor", 
      "GSK-3 inhibitors", 
      "Western blotting", 
      "expression patterns", 
      "cell apoptosis", 
      "RT-PCR", 
      "BrdU incorporation", 
      "Bcl-2", 
      "survival", 
      "cell proliferation", 
      "Recent evidence", 
      "new markers", 
      "molecule inhibitors", 
      "carcinoma", 
      "cell lines", 
      "cancer", 
      "inhibition", 
      "proliferation", 
      "apoptotic threshold", 
      "subsequent increase", 
      "inhibitors", 
      "RNA interference", 
      "cytosolic fractionation", 
      "new promising approach", 
      "chemotherapy", 
      "cells", 
      "docetaxel", 
      "immunohistochemistry", 
      "expression", 
      "blotting", 
      "treatment", 
      "apoptosis", 
      "markers", 
      "accumulation", 
      "NF", 
      "effect", 
      "XIAP", 
      "promising approach", 
      "evidence", 
      "MTS", 
      "patterns", 
      "target", 
      "inactivation", 
      "factors", 
      "decrease", 
      "regulation", 
      "increase", 
      "objective", 
      "results", 
      "threshold", 
      "lines", 
      "molecules", 
      "part", 
      "incorporation", 
      "fractionation", 
      "approach", 
      "interference"
    ], 
    "name": "Glycogen synthase kinase-3: a new therapeutic target in renal cell carcinoma", 
    "pagination": "2005-2014", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1016108440"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/sj.bjc.6605437"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "19920820"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/sj.bjc.6605437", 
      "https://app.dimensions.ai/details/publication/pub.1016108440"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-10-01T06:35", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20221001/entities/gbq_results/article/article_482.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1038/sj.bjc.6605437"
  }
]
 

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.10.1038/sj.bjc.6605437'

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

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/sj.bjc.6605437'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/sj.bjc.6605437'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/sj.bjc.6605437'


 

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

340 TRIPLES      21 PREDICATES      146 URIs      129 LITERALS      26 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/sj.bjc.6605437 schema:about N062eee6a848446629fca7dcce0d6a936
2 N0df151759a03424baf989992adbe037d
3 N3610e8d1c54f417689fe50e57d40503d
4 N387fb5dc3595426e8590738f5c9e163b
5 N4790b2bd79ef4c0d802e67648d66221b
6 N5001c11169ae41428076c364ad73d49a
7 N53b8374c99a64bc6b189ab8202744915
8 N58ce978de86344f7a60a037598e2b02d
9 N633baff390ec4f4f909cdd58c9aa2c62
10 N76a0be0fe0244647b0d782990f1dbadd
11 N7c40ddbc282d47d5b4f9f183a6c478ba
12 N87b97a0e302f4fcaab8692449595a801
13 Naecf1a0047804278b657ff2d8e1ddee4
14 Nc0cfef9636fe4d05a48b55ce0259aa59
15 Ncbf727a4d704451587895273f7b71039
16 Nd24976580cf34a01a2e6103e0fe449bd
17 Ndc210d0952e3475eb5ac0139568b3c99
18 Nf6783631468b4bb5b2041426a12c7eb4
19 Nfd9adb114eaf4bb0b2cc98747bc29f14
20 anzsrc-for:11
21 anzsrc-for:1112
22 schema:author N07b33b4753124fb29ecdb7f67cae332a
23 schema:citation sg:pub.10.1007/bf02524349
24 sg:pub.10.1038/35017574
25 sg:pub.10.1038/nature07284
26 sg:pub.10.1038/sj.bjc.6603359
27 sg:pub.10.1038/sj.bjc.6604268
28 sg:pub.10.1038/sj.cr.7310078
29 sg:pub.10.1038/sj.onc.1204525
30 sg:pub.10.1038/sj.onc.1208068
31 sg:pub.10.1038/sj.onc.1209346
32 schema:datePublished 2009-11-17
33 schema:datePublishedReg 2009-11-17
34 schema:description Background:Renal cell carcinoma (RCC) is highly resistant to chemotherapy because of a high apoptotic threshold. Recent evidences suggest that GSK-3β positively regulates human pancreatic cancer and leukaemia cell survival in part through regulation of nuclear factor (NF-κB)-mediated expression of anti-apoptotic molecules. Our objectives were to determine the expression pattern of GSK-3β and to assess the anti-cancer effect of GSK-3β inhibition in RCC.Methods:Immunohistochemistry and nuclear/cytosolic fractionation were performed to determine the expression pattern of GSK-3β in human RCCs. We used small molecule inhibitor, RNA interference, western blotting, quantitative RT–PCR, BrDU incorporation and MTS assays to study the effect of GSK-3β inactivation on renal cancer cell proliferation and survival.Results:We detected aberrant nuclear accumulation of GSK-3β in RCC cell lines and in 68 out of 74 (91.89%) human RCCs. We found that pharmacological inhibition of GSK-3 led to a decrease in proliferation and survival of renal cancer cells. We observed that inhibition of GSK-3 results in decreased expression of NF-κB target genes Bcl-2 and XIAP and a subsequent increase in renal cancer cell apoptosis. Moreover, we show that GSK-3 inhibitor and Docetaxel synergistically suppress proliferation and survival of renal cancer cells.Conclusions:Our results show nuclear accumulation of GSK-3β as a new marker of human RCC, identify that GSK-3 positively regulates RCC cell survival and proliferation and suggest inhibition of GSK-3 as a new promising approach in the treatment of human renal cancer.
35 schema:genre article
36 schema:isAccessibleForFree true
37 schema:isPartOf N347748b1601d4f269247cdf96d79a2c7
38 N91c73be8b18e475b9a49709b5d0ef0bc
39 sg:journal.1017082
40 schema:keywords Bcl-2
41 BrdU incorporation
42 GSK-3
43 GSK-3 inhibitors
44 GSK-3 results
45 GSK-3β
46 GSK-3β inactivation
47 GSK-3β inhibition
48 MTS
49 NF
50 RCC cell lines
51 RCC cell survival
52 RNA interference
53 RT-PCR
54 Recent evidence
55 Western blotting
56 XIAP
57 aberrant nuclear accumulation
58 accumulation
59 anti-apoptotic molecules
60 anti-cancer effects
61 apoptosis
62 apoptotic threshold
63 approach
64 blotting
65 cancer
66 cancer cell apoptosis
67 cancer cell proliferation
68 cancer cells
69 carcinoma
70 cell apoptosis
71 cell carcinoma
72 cell lines
73 cell proliferation
74 cell survival
75 cells
76 chemotherapy
77 cytosolic fractionation
78 decrease
79 decreased expression
80 docetaxel
81 effect
82 evidence
83 expression
84 expression patterns
85 factors
86 fractionation
87 gene Bcl-2
88 high apoptotic threshold
89 human pancreatic cancer
90 human renal cancer
91 human renal cell carcinoma
92 immunohistochemistry
93 inactivation
94 incorporation
95 increase
96 inhibition
97 inhibitors
98 interference
99 leukemia cell survival
100 lines
101 markers
102 molecule inhibitors
103 molecules
104 new markers
105 new promising approach
106 new therapeutic targets
107 nuclear accumulation
108 nuclear factor
109 objective
110 pancreatic cancer
111 part
112 patterns
113 pharmacological inhibition
114 proliferation
115 promising approach
116 quantitative RT-PCR
117 regulation
118 renal cancer
119 renal cancer cell apoptosis
120 renal cancer cell proliferation
121 renal cancer cells
122 renal cell carcinoma
123 results
124 small molecule inhibitors
125 subsequent increase
126 suppress proliferation
127 survival
128 target
129 target genes Bcl-2
130 therapeutic target
131 threshold
132 treatment
133 schema:name Glycogen synthase kinase-3: a new therapeutic target in renal cell carcinoma
134 schema:pagination 2005-2014
135 schema:productId N25fbd275e5ee4f34a6a25242ad0fb295
136 N74706dfa6eb7476296995a128f91c1c4
137 N8c93ddcd8e12476f84097e5c41beaa17
138 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016108440
139 https://doi.org/10.1038/sj.bjc.6605437
140 schema:sdDatePublished 2022-10-01T06:35
141 schema:sdLicense https://scigraph.springernature.com/explorer/license/
142 schema:sdPublisher Na429f21195b140b6b0d4a60429e01e7a
143 schema:url https://doi.org/10.1038/sj.bjc.6605437
144 sgo:license sg:explorer/license/
145 sgo:sdDataset articles
146 rdf:type schema:ScholarlyArticle
147 N062eee6a848446629fca7dcce0d6a936 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
148 schema:name Carcinoma, Renal Cell
149 rdf:type schema:DefinedTerm
150 N07b33b4753124fb29ecdb7f67cae332a rdf:first sg:person.01217564427.06
151 rdf:rest N6bf9d24e2f6949519393fcdb1f61da58
152 N0df151759a03424baf989992adbe037d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
153 schema:name Adult
154 rdf:type schema:DefinedTerm
155 N1f9160f4f6fc462aa38ee7c92eca2e96 rdf:first sg:person.0717052177.19
156 rdf:rest N6bf96f1f15c84dba85f2c203a7722705
157 N25fbd275e5ee4f34a6a25242ad0fb295 schema:name pubmed_id
158 schema:value 19920820
159 rdf:type schema:PropertyValue
160 N347748b1601d4f269247cdf96d79a2c7 schema:issueNumber 12
161 rdf:type schema:PublicationIssue
162 N3610e8d1c54f417689fe50e57d40503d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
163 schema:name Female
164 rdf:type schema:DefinedTerm
165 N387fb5dc3595426e8590738f5c9e163b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
166 schema:name Glycogen Synthase Kinase 3
167 rdf:type schema:DefinedTerm
168 N40a3e301343547328819cc9a14a181e3 rdf:first sg:person.0610107330.58
169 rdf:rest rdf:nil
170 N4225384f2228421589af50afbbab6854 rdf:first sg:person.01214063623.55
171 rdf:rest N4e3729e9a11e42b6830409e249caaa90
172 N4227c37a8ba2461db2d24be86acdcb4f rdf:first sg:person.0712650615.38
173 rdf:rest N40a3e301343547328819cc9a14a181e3
174 N4790b2bd79ef4c0d802e67648d66221b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
175 schema:name Thiazoles
176 rdf:type schema:DefinedTerm
177 N4e3729e9a11e42b6830409e249caaa90 rdf:first sg:person.01066211163.29
178 rdf:rest N1f9160f4f6fc462aa38ee7c92eca2e96
179 N5001c11169ae41428076c364ad73d49a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
180 schema:name Taxoids
181 rdf:type schema:DefinedTerm
182 N53b8374c99a64bc6b189ab8202744915 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
183 schema:name Cell Proliferation
184 rdf:type schema:DefinedTerm
185 N58ce978de86344f7a60a037598e2b02d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
186 schema:name X-Linked Inhibitor of Apoptosis Protein
187 rdf:type schema:DefinedTerm
188 N633baff390ec4f4f909cdd58c9aa2c62 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
189 schema:name Aged
190 rdf:type schema:DefinedTerm
191 N6bf96f1f15c84dba85f2c203a7722705 rdf:first sg:person.01167102574.39
192 rdf:rest Nda88bc232dc9434d9529c0ce41a9133b
193 N6bf9d24e2f6949519393fcdb1f61da58 rdf:first sg:person.01176130410.78
194 rdf:rest N76adb4555be244e8818bef3e50b51dd2
195 N74706dfa6eb7476296995a128f91c1c4 schema:name doi
196 schema:value 10.1038/sj.bjc.6605437
197 rdf:type schema:PropertyValue
198 N76a0be0fe0244647b0d782990f1dbadd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
199 schema:name Male
200 rdf:type schema:DefinedTerm
201 N76adb4555be244e8818bef3e50b51dd2 rdf:first sg:person.01077635223.15
202 rdf:rest N4225384f2228421589af50afbbab6854
203 N7c40ddbc282d47d5b4f9f183a6c478ba schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
204 schema:name NF-kappa B
205 rdf:type schema:DefinedTerm
206 N87b97a0e302f4fcaab8692449595a801 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
207 schema:name Glycogen Synthase Kinase 3 beta
208 rdf:type schema:DefinedTerm
209 N8c93ddcd8e12476f84097e5c41beaa17 schema:name dimensions_id
210 schema:value pub.1016108440
211 rdf:type schema:PropertyValue
212 N91c73be8b18e475b9a49709b5d0ef0bc schema:volumeNumber 101
213 rdf:type schema:PublicationVolume
214 Na429f21195b140b6b0d4a60429e01e7a schema:name Springer Nature - SN SciGraph project
215 rdf:type schema:Organization
216 Naecf1a0047804278b657ff2d8e1ddee4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
217 schema:name Docetaxel
218 rdf:type schema:DefinedTerm
219 Nc0cfef9636fe4d05a48b55ce0259aa59 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
220 schema:name Urea
221 rdf:type schema:DefinedTerm
222 Ncbf727a4d704451587895273f7b71039 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
223 schema:name Proto-Oncogene Proteins c-bcl-2
224 rdf:type schema:DefinedTerm
225 Nd24976580cf34a01a2e6103e0fe449bd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
226 schema:name Middle Aged
227 rdf:type schema:DefinedTerm
228 Nda88bc232dc9434d9529c0ce41a9133b rdf:first sg:person.01106206356.85
229 rdf:rest N4227c37a8ba2461db2d24be86acdcb4f
230 Ndc210d0952e3475eb5ac0139568b3c99 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
231 schema:name Cell Survival
232 rdf:type schema:DefinedTerm
233 Nf6783631468b4bb5b2041426a12c7eb4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
234 schema:name Humans
235 rdf:type schema:DefinedTerm
236 Nfd9adb114eaf4bb0b2cc98747bc29f14 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
237 schema:name Kidney Neoplasms
238 rdf:type schema:DefinedTerm
239 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
240 schema:name Medical and Health Sciences
241 rdf:type schema:DefinedTerm
242 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
243 schema:name Oncology and Carcinogenesis
244 rdf:type schema:DefinedTerm
245 sg:journal.1017082 schema:issn 0007-0920
246 1532-1827
247 schema:name British Journal of Cancer
248 schema:publisher Springer Nature
249 rdf:type schema:Periodical
250 sg:person.01066211163.29 schema:affiliation grid-institutes:grid.268394.2
251 schema:familyName Kawazoe
252 schema:givenName H
253 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01066211163.29
254 rdf:type schema:Person
255 sg:person.01077635223.15 schema:affiliation grid-institutes:grid.268394.2
256 schema:familyName Yuuki
257 schema:givenName K
258 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01077635223.15
259 rdf:type schema:Person
260 sg:person.01106206356.85 schema:affiliation grid-institutes:grid.66875.3a
261 schema:familyName Billadeau
262 schema:givenName D
263 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01106206356.85
264 rdf:type schema:Person
265 sg:person.01167102574.39 schema:affiliation grid-institutes:grid.26091.3c
266 schema:familyName Oya
267 schema:givenName M
268 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01167102574.39
269 rdf:type schema:Person
270 sg:person.01176130410.78 schema:affiliation grid-institutes:grid.16753.36
271 schema:familyName Ougolkov
272 schema:givenName A
273 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01176130410.78
274 rdf:type schema:Person
275 sg:person.01214063623.55 schema:affiliation grid-institutes:grid.268394.2
276 schema:familyName Naito
277 schema:givenName S
278 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01214063623.55
279 rdf:type schema:Person
280 sg:person.01217564427.06 schema:affiliation grid-institutes:grid.268394.2
281 schema:familyName Bilim
282 schema:givenName V
283 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01217564427.06
284 rdf:type schema:Person
285 sg:person.0610107330.58 schema:affiliation grid-institutes:grid.268394.2
286 schema:familyName Tomita
287 schema:givenName Y
288 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0610107330.58
289 rdf:type schema:Person
290 sg:person.0712650615.38 schema:affiliation grid-institutes:grid.268394.2
291 schema:familyName Motoyama
292 schema:givenName T
293 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0712650615.38
294 rdf:type schema:Person
295 sg:person.0717052177.19 schema:affiliation grid-institutes:grid.268394.2
296 schema:familyName Muto
297 schema:givenName A
298 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0717052177.19
299 rdf:type schema:Person
300 sg:pub.10.1007/bf02524349 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010667071
301 https://doi.org/10.1007/bf02524349
302 rdf:type schema:CreativeWork
303 sg:pub.10.1038/35017574 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044051571
304 https://doi.org/10.1038/35017574
305 rdf:type schema:CreativeWork
306 sg:pub.10.1038/nature07284 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026377853
307 https://doi.org/10.1038/nature07284
308 rdf:type schema:CreativeWork
309 sg:pub.10.1038/sj.bjc.6603359 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005704871
310 https://doi.org/10.1038/sj.bjc.6603359
311 rdf:type schema:CreativeWork
312 sg:pub.10.1038/sj.bjc.6604268 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033421639
313 https://doi.org/10.1038/sj.bjc.6604268
314 rdf:type schema:CreativeWork
315 sg:pub.10.1038/sj.cr.7310078 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034472744
316 https://doi.org/10.1038/sj.cr.7310078
317 rdf:type schema:CreativeWork
318 sg:pub.10.1038/sj.onc.1204525 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033274710
319 https://doi.org/10.1038/sj.onc.1204525
320 rdf:type schema:CreativeWork
321 sg:pub.10.1038/sj.onc.1208068 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038643342
322 https://doi.org/10.1038/sj.onc.1208068
323 rdf:type schema:CreativeWork
324 sg:pub.10.1038/sj.onc.1209346 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037518369
325 https://doi.org/10.1038/sj.onc.1209346
326 rdf:type schema:CreativeWork
327 grid-institutes:grid.16753.36 schema:alternateName Department of Pathology, Feinberg School of Medicine, Northwestern University, Ward Building 3-140, 303 E. Chicago Avenue, 60611, Chicago, IL, USA
328 schema:name Department of Pathology, Feinberg School of Medicine, Northwestern University, Ward Building 3-140, 303 E. Chicago Avenue, 60611, Chicago, IL, USA
329 rdf:type schema:Organization
330 grid-institutes:grid.26091.3c schema:alternateName Department of Urology, Keio University School of Medicine, Shinano-machi 35, Shinjuku-ku, Tokyo, Japan
331 schema:name Department of Urology, Keio University School of Medicine, Shinano-machi 35, Shinjuku-ku, Tokyo, Japan
332 rdf:type schema:Organization
333 grid-institutes:grid.268394.2 schema:alternateName Department of Human Pathology (Second Department of Pathology), Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-9585, Yamagata, Japan
334 Department of Urology, Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-9585, Yamagata, Japan
335 schema:name Department of Human Pathology (Second Department of Pathology), Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-9585, Yamagata, Japan
336 Department of Urology, Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-9585, Yamagata, Japan
337 rdf:type schema:Organization
338 grid-institutes:grid.66875.3a schema:alternateName Division of Oncology Research, Mayo Clinic College of Medicine, 200 First Street Southwest, 55905, Rochester, MN, USA
339 schema:name Division of Oncology Research, Mayo Clinic College of Medicine, 200 First Street Southwest, 55905, Rochester, MN, USA
340 rdf:type schema:Organization
 




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


...