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The Epithelial Mesenchymal Transition Confers Resistance to the Apoptotic Effects of Transforming Growth Factor β in Fetal Rat Hepatocytes

AuthorsValdés, Francisco; Álvarez, Alberto M.; Locascio, Annamaria; Vega, Sonia; Herrera, Blanca; Fernández, Margarita ; Benito, Manuel; Nieto, M. Ángela ; Fabregat, Isabel
Issue Date2002
PublisherAmerican Association for Cancer Research
CitationMolecular Cancer Research 1(1): 68-78 (2002)
AbstractFetal 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-xL 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.
Description12 páginas, 8 figuras, 1 tabla.
Appears in Collections:(IC) Artículos
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