STAT3 upregulates the protein expression and transcriptional activity of β-catenin in breast cancer

Int J Clin Exp Pathol. 2010 Jul 25;3(7):654-64.

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.

Keywords: BT-474; MCF-7; STAT3; breast cancer; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Breast Neoplasms / genetics*
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Knockdown Techniques
  • Humans
  • Immunohistochemistry
  • Promoter Regions, Genetic
  • STAT3 Transcription Factor / metabolism*
  • Transcription, Genetic
  • Transfection
  • Up-Regulation
  • beta Catenin / biosynthesis*
  • beta Catenin / genetics

Substances

  • STAT3 Transcription Factor
  • STAT3 protein, human
  • beta Catenin