ErbB2 signaling epigenetically suppresses microRNA-205 transcription via Ras/Raf/MEK/ERK pathway in breast cancer.

ABSTRACT: We previously reported that microRNA-205 (miR-205) is downregulated by overexpression of the receptor tyrosine kinase ErbB2 and that ectopic transfection of miR-205 precursor decreases ErbB2 tumorigenicity in soft agar. In this study, we further analyzed the regulatory mechanisms linking ErbB2 overexpression and miR-205 downregulation. In ErbB2-overexpressing breast epithelial cells, miR-205 expression was significantly increased by treatment with MEK inhibitor U0126 or PD98059, Raf-1 inhibitor ZM-336372, and ERK inhibitor SCH772984, but PI3K inhibitor LY294002 and p38 MAPK inhibitor SB203580 had no effect. We established breast epithelial cells overexpressing RafCAAX, a constitutively active form of Raf-1, and showed that overexpression of RafCAAX dramatically reduced miR-205 expression.

SUBMITTER: Hasegawa T 

PROVIDER: S-EPMC5537069 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature