Modulation of HER2 expression by ferulic acid on human breast cancer MCF7 cells

C. J. Chang, J. H. Chiu*, L. M. Tseng, C. H. Chang, T. M. Chien, C. W. Wu, W. Y. Lui

*此作品的通信作者

研究成果: Article同行評審

65 引文 斯高帕斯(Scopus)

摘要

Background: The molecular mechanisms underlying the mitogenic effect of ferulic acid (FA), an active compound derived from Angelica sinensis, have never been elucidated. It was the aim of this study to investigate the proliferative effect of FA on human breast cancer cell lines and to elucidate its modulation mechanism on HER2 expression in MCF7 line. Materials and methods: By using MCF7 (oestrogen receptor-positive; ER+, HER2-low), BT474 (ER+, HER2-high), MDAMB231 (ER-, HER2-low) and SKBR3 (ER-, HER2-high) human breast cancer cell lines as in vitro models, the mitogenic effects of FA were assessed by trypan blue dye exclusion assay and DNA flow cytometry. Ferulic acid-modulated cell signalling and HER2 gene expression were evaluated in MCF7 line by Western blot and real-time RT-PCR analysis. Results: Ferulic acid ER-dependently stimulated cell proliferation on MCF7 cells in a concentration-dependent manner. The HER2 oncogene (one of the prognostic factors of breast cancer) and ESR1 gene (oestrogen receptor-alpha; ERα) transcription were markedly up-regulated by FA treatment. Besides, HER2 signalling and its downstream molecules such as AKT and ERK1/2 were involved in FA-modulated ERα and cyclin D1 synthesis. Addition of anti-HER2 antibody, trastuzumab, abrogated FA-enhanced proliferative effect on MCF7 cells, indicated a positive feedback control for the action of HER2 in this setting. The fact that the ER antagonist blocked most of the FA-up-regulated HER2 expression, and that trastuzumab down-regulated ERα gene expression, suggested a cross-talk between ERα and HER2 signalling on MCF7 cells. Conclusions: The authors' conclude that FA causes human breast cancer cell proliferation by up-regulation of HER2 and ERα expression.

原文English
頁(從 - 到)588-596
頁數9
期刊European Journal of Clinical Investigation
36
發行號8
DOIs
出版狀態Published - 8月 2006

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