MicroRNA-206 expression is down-regulated in estrogen receptor a-positive human breast cancer.

Abstract #3042

There are large-scale molecular differences between estrogen receptor (ER)-positive and ER-negative breast cancers. ERa is essential for estrogen-dependent growth, and its level of expression is a crucial determinant of response to endocrine therapy and prognosis in ER-positive breast cancer. Multiple mechanisms involved in altering ERa gene expression in breast cancer have been identified, including ERa gene amplification as well as transcriptional silencing by DNA methylation of CpG islands within the ERa promoter and mutations within the open reading frame of ERa. However, expression levels of ERa in breast cancer tissues differ widely among patients, and frequently change during disease progression and in response to systemic therapies. Recent evidence has shown that microRNA (miRNA) mutations or mis-expression correlate with various human cancers, and miR-206 is reported to decrease endogenous ERa mRNA and protein levels in human MCF-7 breast cancer cells via two specific target sites within the 3'-untranslated region of the human ERa transcript. In this study, we show that miR-206 expression is markedly decreased in ERa-positive breast cancer tissues assayed by quantitative RT-PCR analysis. We observe that miR-206 expression is inversely correlated with ERa but not ERb mRNA expression and the expression levels of miR-206 are gradually decreased as the score for ERa protein expression increases in breast cancer tissues. Moreover, transfection experiments revealed that introduction of miR-206 into estrogen-dependent MCF-7 cells inhibits cell growth and induces a dose-dependent repression of ERa mRNA levels. Transfection with miR-206 produces a dose-dependent decrease of mRNA expression of ERa-target genes, such as progesterone receptor, cyclin D1 and pS2 in MCF-7 cells. Our results suggest that miR-206 is a key factor for the regulation of ERa expression in development and progression of human breast cancer and could be a novel candidate for endocrine therapy that targets only ERa.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3042.