Inhibition of epithelial to mesenchymal transition in metastatic breast carcinoma cells by c-Src suppression.
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.
Liu
Xiang
X
Peking University, Beijing, China.
Feng
Renqing
R
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008648:Mesoderm / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
C412373:AG 1879; D014408:Biomarkers, Tumor; D015820:Cadherins; C108381:GEMIN2 protein, human; D009419:Nerve Tissue Proteins; D011743:Pyrimidines; D016601:RNA-Binding Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014746:Vimentin; D019061:src-Family Kinases