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

Laura Amicone, Francesca M. Spagnoli, Gerald Späth, Silvia Giordano, Cristina Tommasini, Silvia Bernardini, Veronica De Luca, Carlo Della Rocca, Mary C. Weiss, Paolo M. Comoglio, Marco Tripodi

Research output: Contribution to journalArticle

156 Citations (Scopus)

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 α-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.

Original languageEnglish
Pages (from-to)495-503
Number of pages9
JournalEMBO Journal
Volume16
Issue number3
DOIs
Publication statusPublished - Feb 3 1997

Fingerprint

Liver
Hepatocytes
Apoptosis
Epithelial Cells
Proto-Oncogene Proteins c-met
Cell Polarity
Transformed Cell Line
Hepatocyte Growth Factor
Receptor Protein-Tyrosine Kinases
Catalytic Domain
Transcription Factors
Complementary DNA
Cells
Phenotype

Keywords

  • Apoptosis protection
  • Cell polarity
  • Immortalized hepatocytes
  • Met

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Transgenic expression in the liver of truncated Met blocks apoptosis and permits immortalization of hepatocytes. / Amicone, Laura; Spagnoli, Francesca M.; Späth, Gerald; Giordano, Silvia; Tommasini, Cristina; Bernardini, Silvia; De Luca, Veronica; Della Rocca, Carlo; Weiss, Mary C.; Comoglio, Paolo M.; Tripodi, Marco.

In: EMBO Journal, Vol. 16, No. 3, 03.02.1997, p. 495-503.

Research output: Contribution to journalArticle

Amicone, L, Spagnoli, FM, Späth, G, Giordano, S, Tommasini, C, Bernardini, S, De Luca, V, Della Rocca, C, Weiss, MC, Comoglio, PM & Tripodi, M 1997, 'Transgenic expression in the liver of truncated Met blocks apoptosis and permits immortalization of hepatocytes', EMBO Journal, vol. 16, no. 3, pp. 495-503. https://doi.org/10.1093/emboj/16.3.495
Amicone, Laura ; Spagnoli, Francesca M. ; Späth, Gerald ; Giordano, Silvia ; Tommasini, Cristina ; Bernardini, Silvia ; De Luca, Veronica ; Della Rocca, Carlo ; Weiss, Mary C. ; Comoglio, Paolo M. ; Tripodi, Marco. / Transgenic expression in the liver of truncated Met blocks apoptosis and permits immortalization of hepatocytes. In: EMBO Journal. 1997 ; Vol. 16, No. 3. pp. 495-503.
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