KLF6 inhibits estrogen receptor-mediated cell growth in breast cancer via a c-Src-mediated pathway

Mol Cell Biochem. 2010 Feb;335(1-2):29-35. doi: 10.1007/s11010-009-0237-8. Epub 2009 Aug 26.

Abstract

Estrogen receptors play a key role in breast cancer development and progression. Kruppel-like factor 6 (KLF6) is a tumour-suppressing protein. The aim of this study was to identify the role of KLF6 inhibition in estrogen receptor(alpha) (ERalpha)-elicited breast cancer development. Protein expression levels were examined by western blot analysis and immunoprecipitation was used to analyse interactions between proteins. An MTT assay was used to study cell proliferation. We found that KLF6 mediates cell growth in ERalpha-positive breast cancer cells through interaction with the c-Src protein. This interaction causes inactivation of the Erk and Akt proteins. These pathways are critical for the proliferation and survival of breast cancer cells. We also established that KLF6 could not mediate cell growth in ERalpha-negative cells. We conclude that KLF6 can modulate ERalpha-mediated cell growth in breast cancer cells. The unique role of KLF6 in mediating cell growth in breast cancer cells opens up the possibility of a new therapeutic strategy for treating breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Estrogen Receptor alpha / antagonists & inhibitors*
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism
  • Female
  • Humans
  • Kruppel-Like Factor 6
  • Kruppel-Like Transcription Factors / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins pp60(c-src) / metabolism*
  • RNA Interference
  • Signal Transduction*

Substances

  • Estrogen Receptor alpha
  • KLF6 protein, human
  • Kruppel-Like Factor 6
  • Kruppel-Like Transcription Factors
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins pp60(c-src)