The Epithelial Mesenchymal Transition Confers Resistance to the Apoptotic Effects of Transforming Growth Factor β in Fetal Rat Hepatocytes11 Ministerio de Sanidad y Consumo, Spain (FIS01/0797 to I.F. and FIS01/0985 to M.A.N.) and Comunidad de Madrid, Spain (CAM-08.1/0078/2000 to I.F. and 08.1/0044/2000 to M.A.N.). B. Herrera and A. Locascio were the recipients of fellowships from the Ministerio de Educación y Cultura, Spain and S. Vega from the Fondo de Investigaciones Sanitarias, Spain

• Published in: Molecular cancer research 2002-11, Vol.1 (1), p.68
• Main Authors: Francisco Valdés, Alberto M. Álvarez, Annamaria Locascio, Sonia Vega, Blanca Herrera, Margarita Fernández, Manuel Benito, M. Angela Nieto, Isabel Fabregat
• Format: Article
• Language: English
• ISSN: 1541-7786; 1557-3125

Fetal rat hepatocytes treated with transforming growth factor β (TGF-β) die by apoptosis. However, a subpopulation of them survives and undergoes an epithelial mesenchymal transition (EMT). This transition also occurs upon incubation with fetal bovine serum. We have isolated the subpopulations that undergo EMT (TGF-β-treated-fetal hepatocytes: TβT-FH; serum-treated-fetal hepatocytes: ST-FH) and show that they present high levels of vimentin and Snail expression and lack cytokeratin 18 and E-cadherin. Both TβT-FH and ST-FH cells require mitogens to grow and maintain the response to TGF-β in terms of growth inhibition. However, they lack differentiation markers such as the liver-enriched transcription factors hepatocyte nuclear factor 4 (HNF-4) or HNF-1α and express the progenitor marker OV-6. Interestingly, the EMT process confers them resistance to the apoptotic effect of TGF-β, with cells showing higher levels of active AKT and Bcl-x L than fetal hepatocytes. In summary, these cells are refractory to the apoptotic effects of TGF-β, showing characteristics of liver progenitors and of some hepatocellular carcinoma cells.