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期刊论文
Altered expression of the RON receptor tyrosine kinase in primary human colorectal adenocarcinomas: generation of different splicing RON variants and their oncogenic potential
Oncogene (2003) 22, 186-197,-0001,():
The RON receptor tyrosine kinase is a member of the MET proto-oncogene family that has been implicated in regulating motile-invasive phenotypes in certain types of epithelial cancers.The purpose of this study was to determine if RON expression is altered in primary human colorectal adenocarcinomas.Results from immunohistochemical staining showed that RON is highly expressed in the majority of colorectal adenocarcinomas (29/49 cases). Accumulated RON is also constitutively active with autophosphorylation in tyrosine residues.Moreover, three splicing variants of RON, namely RON△165, RON△160, and RON△155 were detected and cloned from two primary colon cancer samples.The se RON variants were generated by deletions in different regions in extracellular domains of the RON β chain. Functional studies showed that expression of RON△160 or RON△155 in Martin-Darby canine kidney cells resulted in increased cell dissociation (scatter-like activity). RON variants, RON△160 and RON△155, also exerted the ability to induce multiple focus formation and sustain anchorageindependent growth of transfected NIH3T3 cells. Moreover, NIH3T3 cells expressing RON△160 or RON△155 formed tumors in athymic nude mice and colonized in the lungs. These data suggest that RON expression is altered in certain primary colon cancers. Abnorma l accumulation of RON variants may play a role in the progression of certain colorectal cancers in vivo.
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