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Transgenic expression in the liver of truncated Met blocks apoptosis and permits immortalization of hepatocytes

Item Type:Article
Title:Transgenic expression in the liver of truncated Met blocks apoptosis and permits immortalization of hepatocytes
Creators Name:Amicone, L. and Spagnoli, F.M. and Spaeth, G. and Giordano, S. and Tommasini, C. and Bernardini, S. and De Luca, V. and Della Rocca, C. and Weiss, M.C. and Comoglio, P.M. and Tripodi, M.
Abstract: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.
Keywords:Apoptosis Protection, Cell Polarity, Immortalized Hepatocytes, Met, Animals, Mice
Source:EMBO Journal
ISSN:0261-4189
Publisher:Oxford University Press
Volume:16
Number:3
Page Range:495-503
Date:3 February 1997
Official Publication:https://doi.org/10.1093/emboj/16.3.495
PubMed:View item in PubMed

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