Inhibition of Epithelial to Mesenchymal Transition in Metastatic Breast Carcinoma Cells by c-Src Suppression

Acta Biochim Biophys Sin (Shanghai). 2010 Jul;42(7):496-501. doi: 10.1093/abbs/gmq043. Epub 2010 Jun 10.

Abstract

The aberrant activation of c-Src regulates multiple functions during tumor progression. This study was conducted to investigate the role of c-Src suppression in epithelial to mesenchymal transition (EMT) process in human breast carcinoma cells. c-Src suppression by PP2 (a Src-family kinase inhibitor) or small interfering RNA (siRNA) was carried out in MCF-7 and MDA-MB-231 cells. Cell migration was analyzed by wound-healing assay. The transcription and protein levels of EMT markers and transcription factors were evaluated by reverse transcription-PCR and Western blot analysis, respectively. The changed cell morphology was photographed by light microscope. c-Src suppression by PP2 or siRNA reversed the mesenchymal-like phenotype in MDA-MB-231 cells. E-cadherin was upregulated in MCF-7 and MDA-MB-231 cells after c-Src suppression, whereas vimentin was downregulated in MDA-MB-231 cells. Slug and SIP1 were downregulated after c-Src suppression in MCF-7 and MDA-MB-231 cells, whereas Twist was unchanged. These results suggest that c-Src suppression by PP2 or siRNA may inhibit EMT through regulation of different transcription factors in breast carcinoma cells that have different metastatic potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Humans
  • Mesoderm / metabolism*
  • Mesoderm / pathology
  • Neoplasm Metastasis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Pyrimidines / pharmacology
  • RNA Interference
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Snail Family Transcription Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Vimentin / genetics
  • Vimentin / metabolism
  • src-Family Kinases / antagonists & inhibitors
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism*

Substances

  • AG 1879
  • Biomarkers, Tumor
  • Cadherins
  • GEMIN2 protein, human
  • Nerve Tissue Proteins
  • Pyrimidines
  • RNA-Binding Proteins
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Transcription Factors
  • Vimentin
  • src-Family Kinases