p300 modulates the BRCA1 inhibition of estrogen receptor activity

Saijun Fan, Yong Xian Ma, Ren Qi Yuan, Qinghui Meng, Ji An Wang, Itzhak D. Goldberg, Eliot M. Rosen, Chenguang Wang, Richard G. Pestell, Michael Erdos, Paul Webb, Peter J. Kushner

Research output: Contribution to journalArticlepeer-review

133 Scopus citations


We previously reported that expression of the breast cancer susceptibility gene BRCA1 strongly inhibits the transcriptional activity of the estrogen receptor (ER-α) in human breast and prostate cancer cell lines but only weakly inhibits ER-α activity in cervical cancer cells (S. Fan et al., Science (Wash. DC), 284: 1354-1356, 1999). We now report that the ability of BRCA1 to repress ER-α activity correlates with its ability to induce down-regulation of the cellular levels of the transcriptional coactivator p300 in breast and prostate, but not in cervical cancer cells. On the other hand, BRCA1 failed to alter the expression of the CREB binding protein (CBP), the structural and functional homologue of p300, in any of these cell types. Ectopic expression of either p300 or CBP "rescued" (i.e., reversed) the BRCA1 inhibition of ER-α activity, whereas two other nuclear receptor coactivators, the p300/CBP-associated factor (PCAF) and the glucocorticoid receptor-interacting protein-1 (GRIP1), failed to rescue the ER-α activity. The rescue function mapped to the cysteinehistidine rich domain CH3, a region of p300/CBP that we found to interact directly with the conserved COOH-terminal activation domain (AF-2) of ER-α. p300 and ER-α were also found to interact in vivo and to colocalize within the nucleus in breast cancer cells. These findings suggest that the cofactors p300 and CBP modulate the ability of the BRCA1 protein to inhibit ER-α signaling. They further suggest that the BRCA1 inhibition of ER-α activity may be attributable, at least in part, to the down-regulation of p300.

Original languageEnglish (US)
Pages (from-to)141-151
Number of pages11
JournalCancer research
Issue number1
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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