Tumorigenicity of the met proto-oncogene and the gene for hepatocyte growth factor

Sing Rong, Myriam Bodescot, Donald Blair, Joyce Dunn, Toshikazu Nakamura, Kensaku Mizuno, Morag Park, Andrew Chan, Stuart Aaronson, George F. Vande Woude

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311 Scopus citations


The met proto-oncogene is the tyrosine kinase growth factor receptor for hepatocyte growth factor/scatter factor (HGF/SF). It was previously shown that, like the oncogenic tpr-met, the mouse met proto-oncogene transforms NIH 3T3 cells. We have established NIH 3T3 cells stably expressing both human (Methu) and mouse (Metmu) met proto-oncogene products. The protein products are properly processed and appear on the cell surface. NIH 3T3 cells express endogenous mouse HGF/SF mRNA, suggesting an autocrime activation mechanism for transformation by Metmu. However, the tumor-forming activity of Methu in NIH 3T3 cells is very low compared with that of Metmu, but efficient tumorigenesis occurs when Methu and HGF/SFhu are coexpressed. These results are consistent with an autocrine transformation mechanism and suggest further that the endogenous murine factor inefficiently activates the tumorigenic potential of Methu. The tumorigenicity observed with reciprocal chimeric human and mouse receptors that exchange external ligand-binding domains supports this conclusion. We also show that HGF/SFhu expressed in NIH 3T3 cells produces tumors in nude mice.

Original languageEnglish
Pages (from-to)5152-5158
Number of pages7
JournalMolecular and Cellular Biology
Issue number11
StatePublished - Nov 1992
Externally publishedYes


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