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β‐catenin regulates c‐Myc and CDKN1A expression in breast cancer cells
Author(s) -
Xu Jinhua,
Chen Yinghua,
Huo Dezheng,
Khramtsov Andrey,
Khramtsova Galina,
Zhang Chunling,
Goss Kathleen H.,
Olopade Olufunmilayo I.
Publication year - 2016
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22292
Subject(s) - biology , wnt signaling pathway , gene silencing , breast cancer , cancer research , catenin , cell cycle , cancer cell , cancer , microbiology and biotechnology , signal transduction , gene , genetics
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 β‐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 β‐catenin by siRNA in non‐basal‐like breast cancer cells; however, inhibition of β‐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 β‐catenin silencing. Interestingly, inhibiting β‐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 β‐catenin silencing. Our findings suggest that the regulation of c‐Myc in breast cancer cells is dependent on the molecular subtype, and that β‐catenin‐mediated regulation of c‐Myc and p21 may control the balance of cell death and proliferation in breast cancer. © 2015 Wiley Periodicals, Inc.