Regulation of cytochrome P‐450 CYPIA1 gene expression and protooncogene expression by growth factors in primary hepatocytes

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Abstract
The effect of growth factors on the cytochrome P‐450 (CYPIA1) gene expression was studied in primary mouse hepatocytes. Of the three growth factors used, i.e. epidermal growth factor (EGF), transforming growth factor α (TGFα) and insulin, only EGF or TGFα completely blocked CYPIA1 expression in the presence of the CYPIA1 inducer 3‐methylcholanthrene (3‐MC). This repression was not linked to cell cycle progression of the hepatocyte because insulin was active to induce ‘early immediate genes’ and DNA replication as well as EGF/TGFα but failed to suppress CYPIA1 expression. A specific EGF/TGFα receptor‐mediated function may repress CYPIA1 gene expression and contribute to the acquisition of a xenobiotic drug resistance phenotype.