Different point mutations in the met oncogene elicit distinct biological properties.
The MET proto-oncogene, encoding the tyrosine kinase receptor for HGF, controls genetic programs leading to cell growth, invasiveness, and protection from apoptosis. Recently, MET mutations have been identified in hereditary and sporadic forms of papillary renal carcinoma (PRC). Introduction of different naturally occurring mutations into the MET cDNA results in the acquisition of distinct biochemical and biological properties of transfected cells. Some mutations result in a high increase in tyrosine kinase activity and confer transforming ability in focus forming assays. These mutants hyperactivate the Ras signaling pathway. Other mutations are devoid of transforming potential but are effective in inducing protection from apoptosis and sustaining anchorage-independent growth. These Met(PRC) receptors interact more efficiently with the intracellular transducer Pi3Kinase. The reported results show that MET(PRC) mutations can be responsible for malignant transformation through different mechanisms, either by increasing the growth ability of cells or by protecting cells from apoptosis and allowing accumulation of other genetic lesions.-Giordano, S., Maffe, A., Williams, T. A., Artigiani, S., Gual, P., Bardelli, A., Basilico, C., Michieli, P., Comoglio, P. M. Different point mutations in the met oncogene elicit distinct biological properties.
Giordano
S
S
University of Torino, School of Medicine, Institute for Cancer Research and Treatment (IRCC), 10060 Candiolo, Italy. sgiordano@ircc.unito.it
Maffe
A
A
Williams
T A
TA
Artigiani
S
S
Gual
P
P
Bardelli
A
A
Basilico
C
C
Michieli
P
P
Comoglio
P M
PM
D017209:Apoptosis / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004847:Epithelial Cells; D017354:Point Mutation; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D018631:ras Proteins / Q000378:metabolism
D019859:Proto-Oncogene Proteins c-met; D018631:ras Proteins