Overexpression and activation of the RON receptor tyrosine kinase in a panel of human colorectal carcinoma cell lines

RON is a receptor tyrosine kinase belonging to the MET proto-oncogene famil y. The purposes of this study are to determine the expression and activatio n of RON in a panel of human colon carcinoma cell lines. Western blotting s howed that RON is barely detectable in normal and SV-40-transformed colon e pithelial cells, but highly expressed and constitutively activated in sever al colon carcinoma cell lines including Colo201, HT-29, HCT116, and SW837. Moreover, a novel RON variant with a molecular mass of 160 kDa (RON Delta 1 60) was identified from HT-29 cells. The cDNA encoding RON Delta 160 has an in-frame deletion of 109 amino acids in the extracellular domain of the RO N beta chain, which is caused by splicing out of two exons in the RON mRNA. No mutations were found in the kinase domain of the RON gene in five carci noma cell lines screened. By expressing RON in colon epithelial cells, we f ound that BON activation increases cell motile-invasive activities and prot ects cells against apoptotic death. These data suggest that RON expression and activation are deregulated in colon carcinoma cell lines. By abnormal a ctivation of RON, this receptor and its variant may regulate motile-invasiv e phenotypes of certain colon carcinoma cells in vivo. (C) 2000 Academic Pr ess.