期刊
MOLECULAR CARCINOGENESIS
卷 55, 期 5, 页码 431-439出版社
WILEY
DOI: 10.1002/mc.22292
关键词
basal-like breast cancer; -catenin; c-Myc; CDKN1A; Wnt
资金
- National Cancer Institute Cancer Center Breast Cancer SPORE at the University of Chicago
- Breast Cancer Research Foundation
- National Women's Cancer Research Alliance
- Falk Medical Research Trust
- Jianghan University
We previously reported that the Wnt pathway is preferentially activated in basal-like breast cancer. However, the mechanisms by which the Wnt pathway regulates down-stream targets in basal-like breast cancer, and the biological significance of this regulation, are poorly understood. In this study, we found that c-Myc is highly expressed in the basal-like subtype by microarray analyses and immunohistochemical staining. After silencing -catenin using siRNA, c-Myc expression was decreased in non-basal-like breast cancer cells. In contrast, c-Myc mRNA and protein expression were up-regulated in the basal-like breast cancer cell lines. Decreased c-Myc promoter activity was observed after inhibiting -catenin by siRNA in non-basal-like breast cancer cells; however, inhibition of -catenin or over-expression of dominant-negative LEF1 had no effect on c-Myc promoter activity in basal-like breast cancer cell lines. In addition, CDKN1A mRNA and p21 protein expression were significantly increased in all breast cancer cell lines upon -catenin silencing. Interestingly, inhibiting -catenin expression alone did not induce apoptosis in breast cancer cell lines despite c-Myc regulation, but we observed a modest increase of cells in the G1 phase of the cell cycle and decrease of cells in S phase upon -catenin silencing. Our findings suggest that the regulation of c-Myc in breast cancer cells is dependent on the molecular subtype, and that -catenin-mediated regulation of c-Myc and p21 may control the balance of cell death and proliferation in breast cancer. (c) 2015 Wiley Periodicals, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据