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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ni, Min Chen, Yiwen Fei, Teng Li, Dan Lim, Elgene Liu, X. Shirley Brown, Myles |
| Description | Country affiliation: United States Author Affiliation: Ni M ( Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.) |
| Abstract | Androgen-stimulated growth of the molecular apocrine breast cancer subtype is mediated by an androgen receptor (AR)-regulated transcriptional program. However, the molecular details of this AR-centered regulatory network and the roles of other transcription factors that cooperate with AR in the network remain elusive. Here we report a positive feed-forward loop that enhances breast cancer growth involving AR, AR coregulators, and downstream target genes. In the absence of an androgen signal, TCF7L2 interacts with FOXA1 at AR-binding sites and represses the basal expression of AR target genes, including MYC. Direct AR regulation of MYC cooperates with AR-mediated activation of HER2/HER3 signaling. HER2/HER3 signaling increases the transcriptional activity of MYC through phosphorylation of MAD1, leading to increased levels of MYC/MAX heterodimers. MYC in turn reinforces the transcriptional activation of androgen-responsive genes. These results reveal a novel regulatory network in molecular apocrine breast cancers regulated by androgen and AR in which MYC plays a central role as both a key target and a cooperating transcription factor to drive oncogenic growth. |
| File Format | HTM / HTML |
| ISSN | 08909369 |
| e-ISSN | 15495477 |
| DOI | 10.1101/gad.209569.112 |
| Journal | Genes & Development |
| Issue Number | 7 |
| Volume Number | 27 |
| Language | English |
| Publisher | Cold Spring Harbor Laboratory Press |
| Publisher Date | 2013-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Molecular Discipline Biology__semicolon__developmental Discipline Biology__semicolon__genetics__semicolon__cell Discipline Biology Androgens Metabolism Proto-oncogene Proteins C-myc Signal Transduction Breast Neoplasms Pathology Cell Line, Tumor Gene Expression Regulation, Neoplastic Gene Regulatory Networks Genetics Physiology Genome-wide Association Study Hepatocyte Nuclear Factor 3-alpha Protein Binding Receptors, Androgen Transcription Factor 7-like 2 Protein Transcriptional Activation Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Research Support, U.s. Gov't, Non-p.h.s. |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Developmental Biology |
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