Amicone L, Spagnoli F M, Späth G, Giordano S, Tommasini C, Bernardini S, De Luca V, Della Rocca C, Weiss M C, Comoglio P M, Tripodi M
Dipartimento di Biopatologia Umana, Università La Sapienza, Roma, Italy.
EMBO J. 1997 Feb 3;16(3):495-503. doi: 10.1093/emboj/16.3.495.
Hepatocyte growth factor induces proliferation, motility and differentiation of epithelial cells through the tyrosine kinase receptor encoded by the MET protooncogene. The cytoplasmic portion of Met (referred to as cyto-Met) is activated but only weakly transforming. In order to determine the effect of activated Met on hepatocytes, we have targeted truncated Met expression to the liver by incorporating the cDNA into a vector carrying the entire human alpha-1-antitrypsin transcriptional unit. Transgenic expression in the liver of truncated human Met, containing the regulatory and the catalytic cytoplasmic domains, renders hepatocytes constitutively resistant to apoptosis and reproducibly permits immortalization. The emerging stable cell lines are not transformed and maintain a highly differentiated phenotype judged by the retention of epithelial cell polarity and the expression of hepatocyte-enriched transcription factors as well as hepatic products.
肝细胞生长因子通过由原癌基因MET编码的酪氨酸激酶受体诱导上皮细胞的增殖、运动和分化。Met的细胞质部分（称为细胞内Met）被激活，但转化能力较弱。为了确定激活的Met对肝细胞的影响，我们通过将cDNA整合到携带整个人α-1-抗胰蛋白酶转录单元的载体中，将截短的Met表达靶向到肝脏。在肝脏中截短的人Met的转基因表达，包含调节性和催化性细胞质结构域，使肝细胞组成性地抵抗凋亡，并可重复性地实现永生化。新出现的稳定细胞系未发生转化，并通过保留上皮细胞极性、表达富含肝细胞的转录因子以及肝产物来维持高度分化的表型。
