Abstract |
The steroid receptor coactivator p/CIP, also known as SRC-3, is an oncogene commonly amplified in breast and ovarian cancers. p/CIP is known to associate with coactivator arginine methyltransferase 1 ( CARM1) on select estrogen responsive genes. We have shown, using a ChIP-on-chip approach, that in response to stimulation with 17β-estradiol (E2), the p/CIP/ CARM1 complex is recruited to 204 proximal promoters in MCF-7 cells. Many of the complex target genes have been previously implicated in signaling pathways related to oncogenesis. Jak2, a member of the Jak/Stat signaling cascade, is one of the direct E2-dependent targets of the p/CIP/ CARM1 complex. Following E2-treatment, histone modifications at the Jak2 promoter are reflective of a transcriptionally permissive gene, and modest changes in RNA and protein expression lead us to suggest that an additional factor(s) may be required for a more notable transcriptional and functional response. Bioinformatic examination of the 204 proximal promoter sequences of p/CIP/ CARM1 targets supports the idea that transcription factor crosstalk is likely the favored mechanism of E2-dependent p/CIP/ CARM1 complex recruitment. This data may have implications towards understanding the oncogenic role of p/CIP in breast cancer and ultimately allow for the identification of new prognostic indicators and/or viable therapeutic targets.
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Authors | N Coughlan, G Thillainadesan, J Andrews, M Isovic, J Torchia |
Journal | Biochimica et biophysica acta
(Biochim Biophys Acta)
Vol. 1833
Issue 6
Pg. 1463-75
(Jun 2013)
ISSN: 0006-3002 [Print] Netherlands |
PMID | 23434684
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- Biomarkers, Tumor
- CARD Signaling Adaptor Proteins
- Chromatin
- Estrogens
- RNA, Messenger
- STAT1 Transcription Factor
- STAT1 protein, human
- Estradiol
- NCOA3 protein, human
- Nuclear Receptor Coactivator 3
- JAK1 protein, human
- Janus Kinase 1
- CARD11 protein, human
- Guanylate Cyclase
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Topics |
- Biomarkers, Tumor
(genetics, metabolism)
- Breast Neoplasms
(drug therapy, genetics, metabolism)
- CARD Signaling Adaptor Proteins
(genetics, metabolism)
- Chromatin
(genetics)
- Chromatin Immunoprecipitation
- Estradiol
(pharmacology)
- Estrogens
(pharmacology)
- Female
- Gene Expression Regulation, Neoplastic
(drug effects)
- Guanylate Cyclase
(genetics, metabolism)
- Humans
- Janus Kinase 1
(genetics, metabolism)
- Nuclear Receptor Coactivator 3
(genetics, metabolism)
- Oligonucleotide Array Sequence Analysis
- Promoter Regions, Genetic
(genetics)
- Protein Binding
- RNA, Messenger
(genetics)
- Real-Time Polymerase Chain Reaction
- Reverse Transcriptase Polymerase Chain Reaction
- STAT1 Transcription Factor
(genetics, metabolism)
- Signal Transduction
- Transcription, Genetic
- Tumor Cells, Cultured
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