%0 Journal Article
%T Estrogen-repressed genes ¨C key mediators of estrogen action?
%A Simeen Zubairy
%A Steffi Oesterreich
%J Breast Cancer Research
%D 2005
%I BioMed Central
%R 10.1186/bcr1271
%X There are a handful of studies that report estrogen-mediated repression of genes, with some of them also addressing potential mechanisms. For example, the ErbB2 proto-oncogene is repressed by estrogen [2]. This repression seems to result from competition between estrogen-bound ER-¦Á and another transcription factor (most likely activator protein [AP]-2) for the coactivator steroid receptor coactivator (SRC)-1, because overexpression of SRC-1, but not SRC-2 or SRC-3, relieves repression of ErbB2. This gives rise to the question of whether estrogen-mediated repression really involves 'classical' repression, or merely represents a loss of basal transcription caused by squelching (i.e. competition for a limited pool of coactivators) or simple displacement of coactivators.There is some evidence that corepressors can play a role in estrogen-mediated repression of genes. Overexpression of the corepressors SMRT (silencing mediator for retinoid and thyroid hormone receptors) and SAFB1 (scaffold attachment factor B1) enhanced repression of folate receptor-¦Á [3] and E-cadherin [4], respectively. In contrast, none of the ER-¦Á coactivators tested (including SRC family members) affected the repression of folate receptor-¦Á by estrogen [3]. Interestingly, depletion of the corepressor DP97 attenuated the repression of ErbB2 [5]. These data suggest that corepressors are involved in repression, but is this really an active recruitment of corepressors to the promoters of target genes? Clearly, interaction of corepressors with ER-¦Á in the presence of estrogen does not fit the classical model in which estrogen-bound ER-¦Á interacts with coactivators, whereas antiestrogen-bound ER-¦Á preferentially interacts with corepressors. However, based on a few studies showing that some corepressors can bind ER-¦Á in the presence of estrogen and that coactivators and corepressors coexist in complexes, it might be timely to revisit this model.Another open question is whether nonclassical ER-¦Á pathways ar
%U http://breast-cancer-research.com/content/7/4/163