PMID- 1406687 OWN - NLM STAT- MEDLINE DCOM- 19921116 LR - 20211203 IS - 0270-7306 (Print) IS - 1098-5549 (Electronic) IS - 0270-7306 (Linking) VI - 12 IP - 11 DP - 1992 Nov TI - Tumorigenicity of the met proto-oncogene and the gene for hepatocyte growth factor. PG - 5152-8 AB - 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. FAU - Rong, S AU - Rong S AD - ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702. FAU - Bodescot, M AU - Bodescot M FAU - Blair, D AU - Blair D FAU - Dunn, J AU - Dunn J FAU - Nakamura, T AU - Nakamura T FAU - Mizuno, K AU - Mizuno K FAU - Park, M AU - Park M FAU - Chan, A AU - Chan A FAU - Aaronson, S AU - Aaronson S FAU - Vande Woude, G F AU - Vande Woude GF LA - eng GR - N01-CO-74101/CO/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (MAS1 protein, human) RN - 0 (Proto-Oncogene Mas) RN - 0 (Proto-Oncogene Proteins) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) SB - IM MH - 3T3 Cells MH - Amino Acid Sequence MH - Animals MH - Cell Transformation, Neoplastic/*genetics MH - Gene Expression Regulation MH - Hepatocyte Growth Factor/genetics/*physiology MH - Humans MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Molecular Sequence Data MH - Neoplasms, Experimental/genetics MH - Proto-Oncogene Mas MH - Proto-Oncogene Proteins/genetics/*physiology MH - Proto-Oncogene Proteins c-met MH - *Proto-Oncogenes PMC - PMC360449 EDAT- 1992/11/01 00:00 MHDA- 1992/11/01 00:01 PMCR- 1992/11/01 CRDT- 1992/11/01 00:00 PHST- 1992/11/01 00:00 [pubmed] PHST- 1992/11/01 00:01 [medline] PHST- 1992/11/01 00:00 [entrez] PHST- 1992/11/01 00:00 [pmc-release] AID - 10.1128/mcb.12.11.5152-5158.1992 [doi] PST - ppublish SO - Mol Cell Biol. 1992 Nov;12(11):5152-8. doi: 10.1128/mcb.12.11.5152-5158.1992.