REGULATION OF CYTOCHROME-P-450 CYPIA1 GENE-EXPRESSION AND PROTOONCOGENE EXPRESSION BY GROWTH-FACTORS IN PRIMARY HEPATOCYTES

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. © 1990.