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Ligand‐dependent interaction between estrogen receptor α and adenomatous polyposis coli
Author(s) -
Kouzmenko Alexander P.,
Takeyama Kenichi,
Kawasaki Yoshihiro,
Akiyama Tetsu,
Kato Shigeaki
Publication year - 2008
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2008.01200.x
Subject(s) - adenomatous polyposis coli , transactivation , biology , estrogen receptor , cancer research , carcinogenesis , histone , colorectal cancer , receptor , estrogen receptor alpha , suppressor , cancer , transcription factor , gene , genetics , breast cancer
Numerous independent clinical and experimental studies indicate that estrogens confer a protective effect against development of intestinal tumors, however the molecular mechanisms involved remain unclear. Physiological effects of estrogens are predominantly mediated by the action of nuclear estrogen receptors (ERs). A multifunctional protein adenomatous polyposis coli (APC) is a tumor suppressor and thought to act as a gatekeeper in colon tumorigenesis, as loss of function APC mutations trigger the development of colorectal cancer. Here we report that APC physically associates with ERa in the ligand‐dependent manner. We have shown in the endogenous setting that the ligand‐activated ERa recruits APC to the promoters in ER target genes and that increased levels of ER‐dependent recruitment of APC enhances the ER transactivation through stimulation of histone acetylation. Found in majority of human colon tumors APC truncation mutants lost the ability to interact with ER. Thus, here we present the first evidence of a functional interaction between APC and ER that may be accounted for a tumor protective action of estrogens.