Open AccessTumorigenicity of the met proto-oncogene and the gene for hepatocyte growth factor.
Author(s) -
Sing Rong,
Myriam Bodescot,
Donald G. Blair,
Joseph A. Dunn,
Takahiro Nakamura,
Kensaku Mizuno,
M. Park,
Andrew M. Chan,
S A Aaronson,
George F. Vande Woude
Publication year - 1992
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.12.11.5152
Subject(s) - autocrine signalling , hepatocyte growth factor , biology , 3t3 cells , oncogene , receptor tyrosine kinase , cancer research , growth factor , carcinogenesis , paracrine signalling , microbiology and biotechnology , signal transduction , receptor , cell , cell cycle , cell culture , transfection , gene , genetics
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 autocrine 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.