PPARgamma inhibits the expression of c-MET in human gastric cancer cells through the suppression of Ets.

Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) is shown to inhibit the growth of MKN-45 cells, a human gastric cancer cell line, which overexpresses c-Met tyrosine kinase. The aim of the present study was to investigate whether PPARgamma regulates the expression of c-Met. Two days after the activation of PPARgamma by troglitazone, a potent and selective PPARgamma ligand, a dramatic reduction of c-MET transcripts and the c-Met protein in MKN45 cells was observed. The luciferase assay showed that the activation of PPARgamma suppressed -249 to +330 c-MET promoter activity, driven by cotransfection of ETS-1 expression vector. These data demonstrate that PPARgamma activation is capable of suppressing Ets-induced c-MET gene transcription. Thus, it is possible that the growth inhibitory effect of PPARgamma on MKN-45 cells is related to the suppression of c-MET transcription. Copyright 1999 Academic Press.