[Molecular mechanisms of regulation of estrogen receptor a expression level in breast cancer]

Estrogen receptor alpha (ERalpha) plays an important role in breast cancer development and progression and thus becomes a useful molecular target for breast cancer therapy. ERalpha is differentially expressed in breast cancer patients. Moreover, ERalpha expression levels may change at different stages of breast cancer even for the same patient. ERalpha expression is closely associated with the effect of endocrine therapy and prognosis. The mechanisms underlying ERalpha expression are complicated, because ERalpha expression is regulated at different levels, including chromatin, transcriptional, post- transcriptional, translational, and post-translational levels. Many proteins modulate the transcription of ERalpha gene at the chromatin and transcriptional levels through direct or indirect interaction with the ERa promoter. Some microRNAs decrease ERalpha levels possibly by induction of the degradation of ERalpha mRNA and/or repression of the mRNA translation. At the post-translational level, many proteins regulate ERalpha protein levels through ubiquitin-proteosome pathway. This review focuses on molecular mechanisms of regulation of ERalpha expression at different levels.