Original Article STAT3 upregulates the protein expression and transcriptional activity of β-catenin in breast cancer
Hanan Armanious, Pascal Gelebart, John Mackey, Yupo Ma, Raymond Lai
Department of Laboratory Medicine and Pathology, and the Department of Oncology, Cross Cancer Institute and University of Alberta, Edmonton, Alberta, Canada; the Department of Pathology, The State University of New York at Stony Brook, Stony brook, NY, USA Received July 5, 2010, accepted July, 2010, available online July, 2010
Received July 6, 2010; accepted July 23, 2010; available online July 25, 2010
Abstract: The expression of β-catenin detectable by immunohistochemistry has been reported to be prognostically important in breast cancer. In this study, we investigated the mechanism by which β-catenin is regulated in breast cancer cells. Our analysis of the gene promoter of β- catenin revealed multiple putative STAT3 binding sites. In support of the concept that STAT3 is a transcriptional regulator for β-catenin, results from our chromatin immunoprecipitation studies showed that STAT3 binds to two of the three potential STAT3-binding sites in the gene promoter of β-catenin (-856 and -938). Using our generated MCF-7 cell clones that carry an inducible STAT3C construct, we found that the expression levels of STAT3C significantly correlated with the transcriptional activity of β-catenin. Similar observations were made when we subjected two breast cancer cell lines (MCF-7 and BT-474) to STAT3 knock-down or transient gene transfection of STAT3C. Using immunohistochemistry, we found that pSTAT3 and β-catenin significantly correlated with each other (p=0.003, Fisher`s exact test) in a cohort of primary breast tumors (n=129). To conclude, our results support the concept that STAT3 upregulates the protein expression and transcriptional activity of β-catenin in breast cancer, and these two proteins may cooperate with each other in exerting their oncogenic effects in these tumors.. (IJCEP1007003).
Address all correspondence to: Raymond Lai, MD, PhD Department of Laboratory Medicine and Pathology, Cross Cancer Institute and University of Alberta 11560 University Avenue, Edmonton, Alberta, Canada T6G 1Z2 Telephone: 780-432-8338; Fax: 780-432-8214 E-mail: email@example.com