STAT3 upregulates the protein expression and transcriptional activity of β-catenin in breast cancer.
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.
Armanious
Hanan
H
Department of Laboratory Medicine and Pathology, Cross Cancer Institute and University of Alberta Edmonton, Alberta, Canada.
Gelebart
Pascal
P
Mackey
John
J
Ma
Yupo
Y
Lai
Raymond
R
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D011401:Promoter Regions, Genetic; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation; D051176:beta Catenin / Q000096:biosynthesis* / Q000235:genetics
D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051176:beta Catenin