Support of a bi-faceted role of estrogen receptor ? (ER?) in ER?-positive breast cancer cells.

ABSTRACT: The expression of estrogen receptor ? (ER?) in breast cancer identifies patients most likely to respond to endocrine treatment. The second ER, ER?, is also expressed in breast tumors, but its function and therapeutic potential need further study. Although in vitro studies have established that ER? opposes transcriptional and proliferative functions of ER?, several clinical studies report its correlation with proliferative markers and poorer prognosis. The data demonstrate that ER? opposes ER? are primarily based on transient expression of ER?. Here, we explored the functions of constitutively expressed ER? in ER?-positive breast cancer lines MCF7 and T47D. We found that ER?, under these conditions heterodimerized with ER? in the presence and absence of 17?-estradiol, and induced genome-wide transcriptional changes. Widespread anti-ER? signaling was, however, not observed and ER? was not antiproliferative. Tamoxifen antagonized proliferation and ER-mediated gene regulation both in the presence and absence of ER?. In conclusion, ER?'s role in cells adapted to its expression appears to differ from its role in cells with transient expression. Our study is important because it provides a deeper understanding of ER?'s role in breast tumors that coexpress both receptors and supports an emerging bi-faceted role of ER?.

SUBMITTER: Jonsson P 

PROVIDER: S-EPMC3946733 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature