Met overexpression confers HGF-dependent invasive phenotype to human thyroid carcinoma cells in vitro.
The proto-oncogene c-MET encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF), a pleiotropic cytokine controlling growth, survival, motility, invasive migration, and differentiation of epithelial cells. Like several other epithelial neoplasms, thyroid carcinomas have been found to overexpress c-MET at both the mRNA and protein level. The biological relevance of Met overexpression to thyroid carcinoma natural history, however, remains to be elucidated. Therefore, we analyzed Met expression and response to HGF in two cell lines established from human thyroid carcinomas. In both lines we observed that the overexpressed and constitutively tyrosine phosphorylated HGF receptor maintained biochemical responsiveness to the ligand. Both cell lines were also found to respond to HGF by consistently increasing their motility and invading in vitro reconstituted basal membranes. Conversely, no effect of HGF could be observed in proliferation and survival assays. These data show that overexpression of Met specifically confers to transformed thyroid cells a motile-invasive phenotype that is dependent on exogenous HGF stimulation.
de Luca
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A
Institute for Cancer Research (I.R.C.C.), University of Torino School of Medicine, Italy.
Arena
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N
Sena
L M
LM
Medico
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E
D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000503:physiopathology*; D010641:Phenotype; D010766:Phosphorylation; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D014443:Tyrosine / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D014443:Tyrosine; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met