Spec. Issue 2006 - Article Summary

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Engineering human hepatoma cells with key transcription factors to generate metabolically competent hepatic models

Celia P. Martínez-Jiménez1, María J. Gómez-Lechón1, José V. Castell1,2 and Ramiro Jover1,2
1Unidad de Hepatología Experimental, Centro de Investigación, Hospital Universitario La Fe and 2Departamento de Bioquímica, Facultad de Medicina, Universidad de Valencia, Valencia, Spain.
Because of the intrinsic variability and limited accessibility of primary cultured human hepatocytes, other cell models (e.g. cell lines) have been considered in drug metabolism studies. Unfortunately, hepatic cell lines express only marginal levels of drug-metabolising
cytochrome P450s (CYPs) and are not a real alternative. Lack of CYP expression in hepatomas appears to be the consequence of an altered expression of liver-enriched transcription factors and co-regulators. We have attempted to up-regulate CYP expression by transfecting hepatoma cells with selected factors. Re-expression of one or several of these factors proved to be effective in re-activating different CYPs, and supports the notion that this can be an appropriate strategy to achieve metabolically competent cell lines.

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