Abstract:
: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.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Xu J,Chen Y,Huo D,Khramtsov A,Khramtsova G,Zhang C,Goss KH,Olopade OIdoi
10.1002/mc.22292subject
Has Abstractpub_date
2016-05-01 00:00:00pages
431-9issue
5eissn
0899-1987issn
1098-2744journal_volume
55pub_type
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journal_title:Molecular carcinogenesis
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journal_title:Molecular carcinogenesis
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更新日期:2012-01-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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更新日期:1999-12-01 00:00:00
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更新日期:2014-10-01 00:00:00
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pub_type: 杂志文章
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更新日期:2015-12-01 00:00:00
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更新日期:2015-04-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
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更新日期:2014-01-01 00:00:00
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更新日期:2009-04-01 00:00:00