| | |  | | | | Record from Web of Science® | | | | | | |
| Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor |
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| Author(s): Mazumdar A, Wang RA, Mishra SK, Adam L, Bagheri-Yarmand R, Mandal M, Vadlamudi RK, Kumar R |
| Source: NATURE CELL BIOLOGY Volume: 3 Issue: 1 Pages: 30-37 Published: JAN 2001 |
| Times Cited: 163 References: 40 |
| Abstract: Activation of the heregulin/HER2 pathway in oestrogen receptor (ER)-positive breast-cancer cells leads to suppression of oestrogen-receptor element (ERE)-driven transcription and disruption of oestradiol responsiveness, and thus contributes to progression of tumours to more invasive phenotypes. Here we report the identification of metastatic-associated protein 1 (MTA1), a component of histone deacetylase (HDAC) and nucleosome-remodelling complexes, as a gene product induced by heregulin-beta1 (HRG). Stimulation of cells with HRG is accompanied by suppression of histone acetylation and enhancement of deacetylase activity. MTA1 is also a potent corepressor of ERE transcription, as it blocks the ability of oestradiol to stimulate ER-mediated transcription. The histone-deacetylase inhibitor trichostatin A blocks MTA1-mediated repression of ERE transcription, Furthermore, MTA1 directly interacts with histone deacetylase-l and -2 and with the activation domain of ER-alpha. Overexpression of MTA1 in breast-cancer cells is accompanied by enhancement of the ability of cells to invade and to grow in an anchorage-independent manner. HRG also promotes interaction of MTA1 with endogenous ER and association of MTA1 or HDAC with ERE-responsive target-gene promoters in vivo. These results identify ER-mediated transcription as a nuclear target of MTA1 and indicate that HDAC complexes associated with the MTA1 corepressor may mediate ER transcriptional repression by HRG. |
| Document Type: Article |
| Language: English |
| Reprint Address: Kumar, R (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA |
Addresses:
1. Univ Texas, MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA |
| Publisher: MACMILLAN PUBLISHERS LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Cell Biology |
| IDS Number: 387XD |
| ISSN: 1465-7392 |
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