Rong S, Donehower L A, Hansen M F, Strong L, Tainsky M, Jeffers M, Resau J H, Hudson E, Tsarfaty I, Vande Woude G F
ABL Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA.
Cancer Res. 1995 May 1;55(9):1963-70.
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.
肝细胞生长因子/分散因子的受体Met的不适当表达，已通过自分泌机制与肉瘤发生相关联。肉瘤在李-弗劳梅尼综合征患者以及p53缺陷小鼠中高发。在此我们表明，这些肿瘤表达高水平的Met。此外，从p53缺陷动物建立的传代后期成纤维细胞系过度表达Met，并且在无胸腺裸鼠中具有致瘤性，这表明在体外发生了进展。肿瘤外植体显示肝细胞生长因子/分散因子表达增加以及Met周转加快，表明自分泌Met激活促进肿瘤进展。因此，野生型p53的缺失似乎极大地增加了Met不适当表达的机会。p53功能的丧失本身不会导致转化，但Met的不适当表达可能是肉瘤发生中的一个重要因素。
