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Global gene repression by the steroid receptor coactivator SRC-1 promotes oncogenesis.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Walsh, Claire A. Bolger, Jarlath C. Byrne, Christopher C. Cocchiglia, Sinéad Hao, Yawei Fagan, Aílis Qin, Li Cahalin, Aoife McCartan, Damian McIlroy, Marie Ó'Gaora, Peadar Xu, Jianming Hill, Arnold David Young, Leonie S. |
| Copyright Year | 2014 |
| Abstract | Transcriptional control is the major determinant of cell fate. The steroid receptor coactivator (SRC)-1 enhances the activity of the estrogen receptor in breast cancer cells, where it confers cell survival benefits. Here, we report that a global analysis of SRC-1 target genes suggested that SRC-1 also mediates transcriptional repression in breast cancer cells. Combined SRC-1 and HOXC11 ChIPseq analysis identified the differentiation marker, CD24, and the apoptotic protein, PAWR, as direct SRC-1/HOXC11 suppression targets. Reduced expression of both CD24 and PAWR was associated with disease progression in patients with breast cancer, and their expression was suppressed in metastatic tissues. Investigations in endocrine-resistant breast cancer cell lines and SRC-1(-/-)/PyMT mice confirmed a role for SRC-1 and HOXC11 in downregulation of CD24 and PAWR. Through bioinformatic analysis and liquid chromatography/mass spectrometry, we identified AP1 proteins and Jumonji domain containing 2C (JMD2C/KDM4C), respectively, as members of the SRC-1 interactome responsible for transcriptional repression. Our findings deepen the understanding of how SRC-1 controls transcription in breast cancers. |
| Starting Page | 131 |
| Ending Page | 137 |
| Page Count | 7 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://cancerres.aacrjournals.org/content/canres/early/2014/04/14/0008-5472.CAN-13-2133.full.pdf |
| Alternate Webpage(s) | http://cancerres.aacrjournals.org/content/canres/early/2014/03/19/0008-5472.CAN-13-2133.full.pdf |
| Alternate Webpage(s) | http://cancerres.aacrjournals.org/content/canres/74/9/2533.full.pdf |
| PubMed reference number | 24648347v1 |
| Alternate Webpage(s) | https://doi.org/10.1158/0008-5472.CAN-13-2133 |
| DOI | 10.1158/0008-5472.can-13-2133 |
| Journal | Cancer research |
| Volume Number | 74 |
| Issue Number | 9 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Antigens, CD24 Bio-Informatics Body tissue Cell Survival Down-Regulation Estrogens HOXC11 gene Interleukin Receptor Common gamma Subunit KDM4C gene Leukemia, B-Cell Liquid Chromatography Mass Spectrometry Mammary Neoplasms NCOA1 protein, human PAWR gene PAWR protein, human Paget's Disease, Mammary Patients Receptors, Steroid Repression, Psychology Steroids Transcription, Genetic Transcriptional Regulation Transcriptional Repression benefit cancer cell estrogen receptor alpha, human |
| Content Type | Text |
| Resource Type | Article |
