c-Myc and Max interactions in quiescent and mitogen-stimulated primary hepatocytes.
The c-myc oncogene has been linked with cell proliferation, apoptosis, and differentiation, and when its expression is deregulated also with malignant transformation. In primary hepatocytes c-myc expression is constitutive and in part regulated by hepatocyte-specific growth factors (HGF, TGFalpha, and EGF) in a delayed early response manner. Max expression in these cells was found to be constitutive throughout the in vitro lifetime and mRNA transcript levels were increased at 12 h after induction with growth factors. Max was found to be associated in vivo with hepatocyte Myc species, with this association being independent of growth conditions and of the endogenous Myc or Max levels. Inhibition of endogenous hepatocyte Max levels via expression of an antisense max construct driven by the MMTV promoter did not affect the DNA synthetic response in the presence of dHGF (a variant of HGF). The unusually long half-life of the endogenous Myc species was found to be independent of their association with the widely accepted as "stable" partner, Max. We suggest that Myc and Max in hepatocytes are involved in the growth (proliferation, cell death) and differentiation program of these cells, acting independently or as a complex.
Skouteris
G G
GG
Division of Virus-Host Cell Interactions, Deutsches Krebsforschungszentrum, Research Program Applied Tumour Virology, Heidelberg, Germany. g.skouteris@dkfz-heidelberg.de
Schröder
C H
CH
D000818:Animals; D000918:Antibody Specificity; D016375:Antisense Elements (Genetics); D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D002478:Cells, Cultured / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D004247:DNA / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D008297:Male; D008934:Mitogens / Q000494:pharmacology*; D010455:Peptides / Q000032:analysis / Q000276:immunology; D011233:Precipitin Tests; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000276:immunology
D016375:Antisense Elements (Genetics); D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C499329:Max protein, rat; D008934:Mitogens; C067850:Myc associated factor X; D010455:Peptides; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D017228:Hepatocyte Growth Factor; D004247:DNA