Met proto-oncogene product is overexpressed in tumors of p53-deficient mice and tumors of Li-Fraumeni patients - PubMed

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• PMID: 7728766

Met proto-oncogene product is overexpressed in tumors of p53-deficient mice and tumors of Li-Fraumeni patients

S Rong et al. Cancer Res. 1995.

Abstract

Inappropriate expression of Met, the receptor for hepatocyte growth factor/scatter factor, has been implicated in sarcomagenesis via an autocrine mechanism. Sarcomas occur at high frequency in individuals with Li-Fraumeni syndrome as well as in p53-deficient mice. Here we show that these tumors express high levels of Met. Moreover, late passage fibroblast cell lines established from p53-deficient animals overexpress Met and can be tumorigenic in athymic nude mice, suggesting that progression occurs in vitro. The tumor explants display increased hepatocyte growth factor/scatter factor expression and Met turnover, indicating that autocrine Met activation contributes to tumor progression. Thus, the loss of wild-type p53 appears to greatly enhance the opportunity for inappropriate Met expression. Loss of p53 function does not by itself cause transformation, but inappropriate Met expression may be an important factor in sarcomagenesis.

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