Upstream determinants of estrogen receptor-alpha regulation of metastatic tumor antigen 3 pathway.

ABSTRACT: Although recent studies have shown a role of estrogen receptor-alpha (ER) in the regulation of epithelial-to-mesenchymal transition via MTA3, the role of upstream determinants of ER regulation of MTA3 and the underlying molecular mechanism remains unknown. Here we show that MTA3 gene regulation by ER is influenced by dynamic changes in levels of nuclear coregulators. MTA3 promoter has a functional ER element half-site with which MTA1 and HDACs interact under basal conditions. Upon estrogen stimulation, these corepressors are derecruited with concomitant recruitment of ER, leading to increased MTA3 transcription and expression. Genetic inactivation of MTA1 pathway promotes the ability of ER to up-regulate MTA3 expression, whereas knockdown of ER enhances MTA1 association with MTA3 gene. Mod

SUBMITTER: Mishra SK 

PROVIDER: S-EPMC1262658 | biostudies-literature | 2004 Jul

REPOSITORIES: biostudies-literature