title: β-catenin regulates c-Myc and CDKN1A expression in breast cancer cells.
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.
authors: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago,, Illinois.|School of Medicine, Jianghan University, Wuhan, Hubei, P. R. China.
authors: Jinhua
authors: J
authors: Xu
authors: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago,, Illinois.
authors: Yinghua
authors: Y
authors: Chen
authors: Department of Public Health Sciences, University of Chicago, Chicago, Illinois.
authors: Dezheng
authors: D
authors: Huo
authors: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago,, Illinois.
authors: Andrey
authors: A
authors: Khramtsov
authors: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago,, Illinois.
authors: Galina
authors: G
authors: Khramtsova
authors: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago,, Illinois.
authors: Chunling
authors: C
authors: Zhang
authors: University of Chicago Comprehensive Cancer Center, University of Chicago, Chicago, Illinois.
authors: Kathleen H
authors: KH
authors: Goss
authors: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago,, Illinois.|Department of Human Genetics, University of Chicago, Chicago, Illinois.
authors: Olufunmilayo I
authors: OI
authors: Olopade
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D061986:MCF-7 Cells; D011401:Promoter Regions, Genetic / Q000187:drug effects; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D051176:beta Catenin
keywords: CDKN1A; Wnt; basal-like breast cancer; c-Myc; β-catenin