Regulation of cytochrome P-450 CYPIA1 gene expression and proto-oncogene 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 alpha (TGF alpha) and insulin, only EGF or TGF alpha 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/TGF alpha but failed to suppress CYPIA1 expression. A specific EGF/TGF alpha receptor-mediated function may repress CYPIA1 gene expression and contribute to the acquisition of a xenobiotic drug resistance phenotype.
Höhne
M
M
Institute of Pharmacology and Toxicology, University of Göttingen, FRG.
Becker-Rabbenstein
V
V
Kahl
G F
GF
Taniguchi
H
H
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005796:Genes / Q000187:drug effects*; D006133:Growth Substances / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011519:Proto-Oncogenes / Q000187:drug effects*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D016211:Transforming Growth Factor alpha / Q000494:pharmacology
D004268:DNA-Binding Proteins; D006133:Growth Substances; D007328:Insulin; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D016211:Transforming Growth Factor alpha; D008748:Methylcholanthrene; D004815:Epidermal Growth Factor; D003577:Cytochrome P-450 Enzyme System; D011505:Protein-Tyrosine Kinases