Estrogen-related receptors alpha, beta and gamma expression and function is associated with transcriptional repressor EZH2 in breast carcinoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Kanchan Kumari, Amit K. Adhya, Arabinda Kumar Rath, P. B. Reddy, Sandip K. Mishra

ABSTRACT

BACKGROUND: Orphan nuclear receptors ERRα, ERRβ and ERRγ that belong to NR3B or type IV nuclear receptor family are well studied for their role in breast cancer pathophysiology. Their homology with the canonical estrogen receptor dictates their possible contributing role in mammary gland development and disease. Although function and regulation of ERRα, ERRγ and less about ERRβ is reported, role of histone methylation in their altered expression in cancer cells is not studied. Transcriptional activity of nuclear receptors depends on co-regulatory proteins. The present study for the first time gives an insight into regulation of estrogen-related receptors by histone methylation specifically through methyltransferase EZH2 in breast cancer. METHODS: Expression of ERRα, ERRβ, ERRγ and EZH2 was assessed by immunohistochemistry in four identical tissue array slides that were prepared as per the protocol. The array slides were stained with ERRα, ERRβ, ERRγ and EZH2 simultaneously. Array data was correlated with expression in MERAV expression dataset. Pearson correlation coeficient r was calculated from the partial matrix expression values available at MERAV database to study the strength of association between EZH2 and three orphan nuclear receptors under study. By western blot and real time PCR, their correlated expression was studied in breast cancer cell lines MCF-7, MDA-MB-231, T47D and MDA-MB-453 including normal breast epithelial MCF-10A cells at both protein and RNA level. Regulation of ERRα, ERRβ, ERRγ by EZH2 was further investigated upon overexpression and silencing of EZH2. The interaction between ERRs and EZH2 was validated in vivo by CHIP-qPCR. RESULTS: We found a negative correlation between estrogen-related receptors and Enhancer of Zeste Homolog 2, a global repressor gene. Immunohistochemistry in primary breast tumors of different grades showed a correlated expression of estrogen-related receptors and EZH2. Their correlated expression was further validated using online MERAV expression dataset where a negative correlation of variable strengths was observed in breast cancer. Ectopic expression of EZH2 in low EZH2-expressing normal breast epithelial cells abrogated their expression and at the same time, its silencing enhanced the expression of estrogen-related receptors in cancerous cells. Global occupancy of EZH2 on ERRα and ERRβ was observed in-vivo. CONCLUSION: Our findings identify EZH2 as a relevant coregulator for estrogen-related receptors in breast carcinoma. More... »

PAGES

690

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12885-018-4586-0

DOI

http://dx.doi.org/10.1186/s12885-018-4586-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1105110830

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29940916


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/2008/1112", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Oncology and Carcinogenesis", 
        "type": "DefinedTerm"
      }, 
      {
        "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"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Institute of Life Sciences", 
          "id": "https://www.grid.ac/institutes/grid.418782.0", 
          "name": [
            "Cancer Biology Laboratory, Department of Gene Function and Regulation, Institute of Life Sciences, Bhubaneswar. Utkal University, Bhubaneswar, Odisha, India"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kumari", 
        "givenName": "Kanchan", 
        "id": "sg:person.014025345255.09", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014025345255.09"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "name": [
            "Department of Pathology, AIIMS, Bhubaneswar, Odisha, India"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Adhya", 
        "givenName": "Amit K.", 
        "id": "sg:person.01353070554.93", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01353070554.93"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "name": [
            "Hemalata Hospitals, Chandrashekharpur, Bhubaneswar, Odisha, India"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Rath", 
        "givenName": "Arabinda Kumar", 
        "id": "sg:person.014274204512.12", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014274204512.12"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "name": [
            "Department of Microbiology and Biotechnology, Govt. PG College Ratlam, Ratlam, MP, India"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Reddy", 
        "givenName": "P. B.", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institute of Life Sciences", 
          "id": "https://www.grid.ac/institutes/grid.418782.0", 
          "name": [
            "Cancer Biology Laboratory, Department of Gene Function and Regulation, Institute of Life Sciences, Bhubaneswar. Utkal University, Bhubaneswar, Odisha, India"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Mishra", 
        "givenName": "Sandip K.", 
        "id": "sg:person.0670736534.36", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0670736534.36"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1091/mbc.e15-07-0512", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003670280"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m202952200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003891688"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1101/pdb.prot5439", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004633720"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.neurobiolaging.2016.09.013", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005505602"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1677/erc-08-0305", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006535196"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2147/cmar.s35024", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006720109"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/srep17621", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007023727", 
          "https://doi.org/10.1038/srep17621"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-08-1594", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007356845"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrd3674", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007920084", 
          "https://doi.org/10.1038/nrd3674"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1101/pdb.prot5279", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008176950"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/bioinformatics/bti398", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009073359"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.celrep.2015.12.086", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010553721"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/gb-2005-6-8-r65", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018510112", 
          "https://doi.org/10.1186/gb-2005-6-8-r65"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/bjc.2014.53", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021174473", 
          "https://doi.org/10.1038/bjc.2014.53"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1046/j.1365-2559.1999.00632.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022195546"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrg.2016.93", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022900088", 
          "https://doi.org/10.1038/nrg.2016.93"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/73432", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024393583", 
          "https://doi.org/10.1038/73432"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/73432", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024393583", 
          "https://doi.org/10.1038/73432"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-06-3855", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024669511"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-10-1315", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024903647"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-08-3062", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026254734"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1677/jme.1.01586", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029237948"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/bmb.20999", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029254860"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/bmb.20999", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029254860"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1541-7786.mcr-06-0227", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030370040"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/bcr3124", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030616191", 
          "https://doi.org/10.1186/bcr3124"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc3396", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031306051", 
          "https://doi.org/10.1038/nrc3396"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1210986", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031892019", 
          "https://doi.org/10.1038/sj.onc.1210986"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1101/pdb.prot086280", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032885125"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s12943-016-0502-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033255466", 
          "https://doi.org/10.1186/s12943-016-0502-x"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.bbadis.2015.06.016", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034158900"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-11-1431", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036104104"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1621/nrs.14002", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043323400"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1940-6207.capr-11-0414", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043483218"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncomms3126", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043513580", 
          "https://doi.org/10.1038/ncomms3126"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s1046-2023(03)00032-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045111385"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s1046-2023(03)00032-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045111385"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s1046-2023(03)00032-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045111385"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1210/er.20.5.689", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1064285753"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1074881956", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1075192374", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2018-12", 
    "datePublishedReg": "2018-12-01", 
    "description": "BACKGROUND: Orphan nuclear receptors ERR\u03b1, ERR\u03b2 and ERR\u03b3 that belong to NR3B or type IV nuclear receptor family are well studied for their role in breast cancer pathophysiology. Their homology with the canonical estrogen receptor dictates their possible contributing role in mammary gland development and disease. Although function and regulation of ERR\u03b1, ERR\u03b3 and less about ERR\u03b2 is reported, role of histone methylation in their altered expression in cancer cells is not studied. Transcriptional activity of nuclear receptors depends on co-regulatory proteins. The present study for the first time gives an insight into regulation of estrogen-related receptors by histone methylation specifically through methyltransferase EZH2 in breast cancer.\nMETHODS: Expression of ERR\u03b1, ERR\u03b2, ERR\u03b3 and EZH2 was assessed by immunohistochemistry in four identical tissue array slides that were prepared as per the protocol. The array slides were stained with ERR\u03b1, ERR\u03b2, ERR\u03b3 and EZH2 simultaneously. Array data was correlated with expression in MERAV expression dataset. Pearson correlation coeficient r was calculated from the partial matrix expression values available at MERAV database to study the strength of association between EZH2 and three orphan nuclear receptors under study. By western blot and real time PCR, their correlated expression was studied in breast cancer cell lines MCF-7, MDA-MB-231, T47D and MDA-MB-453 including normal breast epithelial MCF-10A cells at both protein and RNA level. Regulation of ERR\u03b1, ERR\u03b2, ERR\u03b3 by EZH2 was further investigated upon overexpression and silencing of EZH2. The interaction between ERRs and EZH2 was validated in vivo by CHIP-qPCR.\nRESULTS: We found a negative correlation between estrogen-related receptors and Enhancer of Zeste Homolog 2, a global repressor gene. Immunohistochemistry in primary breast tumors of different grades showed a correlated expression of estrogen-related receptors and EZH2. Their correlated expression was further validated using online MERAV expression dataset where a negative correlation of variable strengths was observed in breast cancer. Ectopic expression of EZH2 in low EZH2-expressing normal breast epithelial cells abrogated their expression and at the same time, its silencing enhanced the expression of estrogen-related receptors in cancerous cells. Global occupancy of EZH2 on ERR\u03b1 and ERR\u03b2 was observed in-vivo.\nCONCLUSION: Our findings identify EZH2 as a relevant coregulator for estrogen-related receptors in breast carcinoma.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1186/s12885-018-4586-0", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1024632", 
        "issn": [
          "1471-2407"
        ], 
        "name": "BMC Cancer", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "18"
      }
    ], 
    "name": "Estrogen-related receptors alpha, beta and gamma expression and function is associated with transcriptional repressor EZH2 in breast carcinoma", 
    "pagination": "690", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "7decaf2f241bc52f13ce837eeb9c34623eb6f81da734ff08a3acb43ae1a6829c"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "29940916"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "100967800"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1186/s12885-018-4586-0"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1105110830"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1186/s12885-018-4586-0", 
      "https://app.dimensions.ai/details/publication/pub.1105110830"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T00:26", 
    "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/v90/0000000001_0000000264/records_8695_00000572.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://link.springer.com/10.1186%2Fs12885-018-4586-0"
  }
]
 

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.10.1186/s12885-018-4586-0'

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

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s12885-018-4586-0'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s12885-018-4586-0'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s12885-018-4586-0'


 

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

221 TRIPLES      21 PREDICATES      66 URIs      21 LITERALS      9 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1186/s12885-018-4586-0 schema:about anzsrc-for:11
2 anzsrc-for:1112
3 schema:author N46dd619f249a49119abc0c18e4532124
4 schema:citation sg:pub.10.1038/73432
5 sg:pub.10.1038/bjc.2014.53
6 sg:pub.10.1038/ncomms3126
7 sg:pub.10.1038/nrc3396
8 sg:pub.10.1038/nrd3674
9 sg:pub.10.1038/nrg.2016.93
10 sg:pub.10.1038/sj.onc.1210986
11 sg:pub.10.1038/srep17621
12 sg:pub.10.1186/bcr3124
13 sg:pub.10.1186/gb-2005-6-8-r65
14 sg:pub.10.1186/s12943-016-0502-x
15 https://app.dimensions.ai/details/publication/pub.1074881956
16 https://app.dimensions.ai/details/publication/pub.1075192374
17 https://doi.org/10.1002/bmb.20999
18 https://doi.org/10.1016/j.bbadis.2015.06.016
19 https://doi.org/10.1016/j.celrep.2015.12.086
20 https://doi.org/10.1016/j.neurobiolaging.2016.09.013
21 https://doi.org/10.1016/s1046-2023(03)00032-x
22 https://doi.org/10.1046/j.1365-2559.1999.00632.x
23 https://doi.org/10.1074/jbc.m202952200
24 https://doi.org/10.1091/mbc.e15-07-0512
25 https://doi.org/10.1093/bioinformatics/bti398
26 https://doi.org/10.1101/pdb.prot086280
27 https://doi.org/10.1101/pdb.prot5279
28 https://doi.org/10.1101/pdb.prot5439
29 https://doi.org/10.1158/0008-5472.can-06-3855
30 https://doi.org/10.1158/0008-5472.can-08-1594
31 https://doi.org/10.1158/0008-5472.can-08-3062
32 https://doi.org/10.1158/0008-5472.can-10-1315
33 https://doi.org/10.1158/0008-5472.can-11-1431
34 https://doi.org/10.1158/1541-7786.mcr-06-0227
35 https://doi.org/10.1158/1940-6207.capr-11-0414
36 https://doi.org/10.1210/er.20.5.689
37 https://doi.org/10.1621/nrs.14002
38 https://doi.org/10.1677/erc-08-0305
39 https://doi.org/10.1677/jme.1.01586
40 https://doi.org/10.2147/cmar.s35024
41 schema:datePublished 2018-12
42 schema:datePublishedReg 2018-12-01
43 schema:description BACKGROUND: Orphan nuclear receptors ERRα, ERRβ and ERRγ that belong to NR3B or type IV nuclear receptor family are well studied for their role in breast cancer pathophysiology. Their homology with the canonical estrogen receptor dictates their possible contributing role in mammary gland development and disease. Although function and regulation of ERRα, ERRγ and less about ERRβ is reported, role of histone methylation in their altered expression in cancer cells is not studied. Transcriptional activity of nuclear receptors depends on co-regulatory proteins. The present study for the first time gives an insight into regulation of estrogen-related receptors by histone methylation specifically through methyltransferase EZH2 in breast cancer. METHODS: Expression of ERRα, ERRβ, ERRγ and EZH2 was assessed by immunohistochemistry in four identical tissue array slides that were prepared as per the protocol. The array slides were stained with ERRα, ERRβ, ERRγ and EZH2 simultaneously. Array data was correlated with expression in MERAV expression dataset. Pearson correlation coeficient r was calculated from the partial matrix expression values available at MERAV database to study the strength of association between EZH2 and three orphan nuclear receptors under study. By western blot and real time PCR, their correlated expression was studied in breast cancer cell lines MCF-7, MDA-MB-231, T47D and MDA-MB-453 including normal breast epithelial MCF-10A cells at both protein and RNA level. Regulation of ERRα, ERRβ, ERRγ by EZH2 was further investigated upon overexpression and silencing of EZH2. The interaction between ERRs and EZH2 was validated in vivo by CHIP-qPCR. RESULTS: We found a negative correlation between estrogen-related receptors and Enhancer of Zeste Homolog 2, a global repressor gene. Immunohistochemistry in primary breast tumors of different grades showed a correlated expression of estrogen-related receptors and EZH2. Their correlated expression was further validated using online MERAV expression dataset where a negative correlation of variable strengths was observed in breast cancer. Ectopic expression of EZH2 in low EZH2-expressing normal breast epithelial cells abrogated their expression and at the same time, its silencing enhanced the expression of estrogen-related receptors in cancerous cells. Global occupancy of EZH2 on ERRα and ERRβ was observed in-vivo. CONCLUSION: Our findings identify EZH2 as a relevant coregulator for estrogen-related receptors in breast carcinoma.
44 schema:genre research_article
45 schema:inLanguage en
46 schema:isAccessibleForFree true
47 schema:isPartOf Nb12bb24f0cea486a884565b91590721e
48 Nbb64aa2770b94c7a91eaa1dd3d8cd817
49 sg:journal.1024632
50 schema:name Estrogen-related receptors alpha, beta and gamma expression and function is associated with transcriptional repressor EZH2 in breast carcinoma
51 schema:pagination 690
52 schema:productId N00a9f3639da44c93bddcf23cb5a3d741
53 N3a07f588c4df4761bd4abf7c0a0967e6
54 N7f8bf19c69d94a5594b3a30d63f90926
55 Nb61e473d9b5d49909642bc1a82caf14a
56 Nffde3978ce0648dc9e4827c80c5f64cd
57 schema:sameAs https://app.dimensions.ai/details/publication/pub.1105110830
58 https://doi.org/10.1186/s12885-018-4586-0
59 schema:sdDatePublished 2019-04-11T00:26
60 schema:sdLicense https://scigraph.springernature.com/explorer/license/
61 schema:sdPublisher N22cde11651724a96baee90e021d4b089
62 schema:url https://link.springer.com/10.1186%2Fs12885-018-4586-0
63 sgo:license sg:explorer/license/
64 sgo:sdDataset articles
65 rdf:type schema:ScholarlyArticle
66 N00a9f3639da44c93bddcf23cb5a3d741 schema:name nlm_unique_id
67 schema:value 100967800
68 rdf:type schema:PropertyValue
69 N22cde11651724a96baee90e021d4b089 schema:name Springer Nature - SN SciGraph project
70 rdf:type schema:Organization
71 N320466c046e943e69fcb849cc5674235 rdf:first sg:person.01353070554.93
72 rdf:rest N865a2a616b224f4fae1fb3929bcf37ce
73 N3a07f588c4df4761bd4abf7c0a0967e6 schema:name doi
74 schema:value 10.1186/s12885-018-4586-0
75 rdf:type schema:PropertyValue
76 N46dd619f249a49119abc0c18e4532124 rdf:first sg:person.014025345255.09
77 rdf:rest N320466c046e943e69fcb849cc5674235
78 N5b8ad8281fc342b994e0e205ec648ce8 schema:name Hemalata Hospitals, Chandrashekharpur, Bhubaneswar, Odisha, India
79 rdf:type schema:Organization
80 N764007ebd1764118b69b0ae16c27b238 rdf:first sg:person.0670736534.36
81 rdf:rest rdf:nil
82 N77beb0a21532467db4ac097fc7ac70a4 schema:name Department of Microbiology and Biotechnology, Govt. PG College Ratlam, Ratlam, MP, India
83 rdf:type schema:Organization
84 N7f8bf19c69d94a5594b3a30d63f90926 schema:name readcube_id
85 schema:value 7decaf2f241bc52f13ce837eeb9c34623eb6f81da734ff08a3acb43ae1a6829c
86 rdf:type schema:PropertyValue
87 N865a2a616b224f4fae1fb3929bcf37ce rdf:first sg:person.014274204512.12
88 rdf:rest N8bbbde837d9540a9b2fd66a12a1a6e91
89 N8bbbde837d9540a9b2fd66a12a1a6e91 rdf:first Nb918b2999e234cdc84a9df62ece11e29
90 rdf:rest N764007ebd1764118b69b0ae16c27b238
91 Nb12bb24f0cea486a884565b91590721e schema:volumeNumber 18
92 rdf:type schema:PublicationVolume
93 Nb2cb3dc7f4304b1596699c409c5bc8ff schema:name Department of Pathology, AIIMS, Bhubaneswar, Odisha, India
94 rdf:type schema:Organization
95 Nb61e473d9b5d49909642bc1a82caf14a schema:name pubmed_id
96 schema:value 29940916
97 rdf:type schema:PropertyValue
98 Nb918b2999e234cdc84a9df62ece11e29 schema:affiliation N77beb0a21532467db4ac097fc7ac70a4
99 schema:familyName Reddy
100 schema:givenName P. B.
101 rdf:type schema:Person
102 Nbb64aa2770b94c7a91eaa1dd3d8cd817 schema:issueNumber 1
103 rdf:type schema:PublicationIssue
104 Nffde3978ce0648dc9e4827c80c5f64cd schema:name dimensions_id
105 schema:value pub.1105110830
106 rdf:type schema:PropertyValue
107 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
108 schema:name Medical and Health Sciences
109 rdf:type schema:DefinedTerm
110 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
111 schema:name Oncology and Carcinogenesis
112 rdf:type schema:DefinedTerm
113 sg:journal.1024632 schema:issn 1471-2407
114 schema:name BMC Cancer
115 rdf:type schema:Periodical
116 sg:person.01353070554.93 schema:affiliation Nb2cb3dc7f4304b1596699c409c5bc8ff
117 schema:familyName Adhya
118 schema:givenName Amit K.
119 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01353070554.93
120 rdf:type schema:Person
121 sg:person.014025345255.09 schema:affiliation https://www.grid.ac/institutes/grid.418782.0
122 schema:familyName Kumari
123 schema:givenName Kanchan
124 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014025345255.09
125 rdf:type schema:Person
126 sg:person.014274204512.12 schema:affiliation N5b8ad8281fc342b994e0e205ec648ce8
127 schema:familyName Rath
128 schema:givenName Arabinda Kumar
129 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014274204512.12
130 rdf:type schema:Person
131 sg:person.0670736534.36 schema:affiliation https://www.grid.ac/institutes/grid.418782.0
132 schema:familyName Mishra
133 schema:givenName Sandip K.
134 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0670736534.36
135 rdf:type schema:Person
136 sg:pub.10.1038/73432 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024393583
137 https://doi.org/10.1038/73432
138 rdf:type schema:CreativeWork
139 sg:pub.10.1038/bjc.2014.53 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021174473
140 https://doi.org/10.1038/bjc.2014.53
141 rdf:type schema:CreativeWork
142 sg:pub.10.1038/ncomms3126 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043513580
143 https://doi.org/10.1038/ncomms3126
144 rdf:type schema:CreativeWork
145 sg:pub.10.1038/nrc3396 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031306051
146 https://doi.org/10.1038/nrc3396
147 rdf:type schema:CreativeWork
148 sg:pub.10.1038/nrd3674 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007920084
149 https://doi.org/10.1038/nrd3674
150 rdf:type schema:CreativeWork
151 sg:pub.10.1038/nrg.2016.93 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022900088
152 https://doi.org/10.1038/nrg.2016.93
153 rdf:type schema:CreativeWork
154 sg:pub.10.1038/sj.onc.1210986 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031892019
155 https://doi.org/10.1038/sj.onc.1210986
156 rdf:type schema:CreativeWork
157 sg:pub.10.1038/srep17621 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007023727
158 https://doi.org/10.1038/srep17621
159 rdf:type schema:CreativeWork
160 sg:pub.10.1186/bcr3124 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030616191
161 https://doi.org/10.1186/bcr3124
162 rdf:type schema:CreativeWork
163 sg:pub.10.1186/gb-2005-6-8-r65 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018510112
164 https://doi.org/10.1186/gb-2005-6-8-r65
165 rdf:type schema:CreativeWork
166 sg:pub.10.1186/s12943-016-0502-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1033255466
167 https://doi.org/10.1186/s12943-016-0502-x
168 rdf:type schema:CreativeWork
169 https://app.dimensions.ai/details/publication/pub.1074881956 schema:CreativeWork
170 https://app.dimensions.ai/details/publication/pub.1075192374 schema:CreativeWork
171 https://doi.org/10.1002/bmb.20999 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029254860
172 rdf:type schema:CreativeWork
173 https://doi.org/10.1016/j.bbadis.2015.06.016 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034158900
174 rdf:type schema:CreativeWork
175 https://doi.org/10.1016/j.celrep.2015.12.086 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010553721
176 rdf:type schema:CreativeWork
177 https://doi.org/10.1016/j.neurobiolaging.2016.09.013 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005505602
178 rdf:type schema:CreativeWork
179 https://doi.org/10.1016/s1046-2023(03)00032-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1045111385
180 rdf:type schema:CreativeWork
181 https://doi.org/10.1046/j.1365-2559.1999.00632.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1022195546
182 rdf:type schema:CreativeWork
183 https://doi.org/10.1074/jbc.m202952200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003891688
184 rdf:type schema:CreativeWork
185 https://doi.org/10.1091/mbc.e15-07-0512 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003670280
186 rdf:type schema:CreativeWork
187 https://doi.org/10.1093/bioinformatics/bti398 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009073359
188 rdf:type schema:CreativeWork
189 https://doi.org/10.1101/pdb.prot086280 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032885125
190 rdf:type schema:CreativeWork
191 https://doi.org/10.1101/pdb.prot5279 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008176950
192 rdf:type schema:CreativeWork
193 https://doi.org/10.1101/pdb.prot5439 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004633720
194 rdf:type schema:CreativeWork
195 https://doi.org/10.1158/0008-5472.can-06-3855 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024669511
196 rdf:type schema:CreativeWork
197 https://doi.org/10.1158/0008-5472.can-08-1594 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007356845
198 rdf:type schema:CreativeWork
199 https://doi.org/10.1158/0008-5472.can-08-3062 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026254734
200 rdf:type schema:CreativeWork
201 https://doi.org/10.1158/0008-5472.can-10-1315 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024903647
202 rdf:type schema:CreativeWork
203 https://doi.org/10.1158/0008-5472.can-11-1431 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036104104
204 rdf:type schema:CreativeWork
205 https://doi.org/10.1158/1541-7786.mcr-06-0227 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030370040
206 rdf:type schema:CreativeWork
207 https://doi.org/10.1158/1940-6207.capr-11-0414 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043483218
208 rdf:type schema:CreativeWork
209 https://doi.org/10.1210/er.20.5.689 schema:sameAs https://app.dimensions.ai/details/publication/pub.1064285753
210 rdf:type schema:CreativeWork
211 https://doi.org/10.1621/nrs.14002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043323400
212 rdf:type schema:CreativeWork
213 https://doi.org/10.1677/erc-08-0305 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006535196
214 rdf:type schema:CreativeWork
215 https://doi.org/10.1677/jme.1.01586 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029237948
216 rdf:type schema:CreativeWork
217 https://doi.org/10.2147/cmar.s35024 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006720109
218 rdf:type schema:CreativeWork
219 https://www.grid.ac/institutes/grid.418782.0 schema:alternateName Institute of Life Sciences
220 schema:name Cancer Biology Laboratory, Department of Gene Function and Regulation, Institute of Life Sciences, Bhubaneswar. Utkal University, Bhubaneswar, Odisha, India
221 rdf:type schema:Organization
 




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


...