Effect of epidermal growth factor on the expression of protooncogenes c-myc and c-Ha-ras in short-term primary hepatocyte culture.
We have characterized the effect of the hepatomitogen epidermal growth factor (EGF) on the expression of the cellular protooncogenes c-Ha-ras and c-myc in short-term (48 hours) primary hepatocyte culture. mRNA concentrations of both protooncogenes increased dramatically in nonproliferating cultures and in the absence of EGF, suggesting that the isolation procedure or the culture conditions may trigger expression of these genes or potentially increase the lifetime of transcripts in vitro, regardless of the presence of a mitogen. In cells treated with EGF, a distinct peak in c-Ha-ras expression was seen 24 hours after EGF treatment. This coincided with the onset of DNA synthesis. No such peak was seen in cultures not treated with EGF. The c-myc mRNA concentrations were increased relatively equally in all cultures with or without the addition of EGF. These data show a differential response of these two cell-cycle-associated genes to the culture conditions and EGF stimulation. It also demonstrated that enhanced gene expression for Ha-ras and myc in hepatocytes can occur in the absence of cell proliferation.
Kost
D P
DP
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.
Michalopoulos
G K
GK
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D008099:Liver / Q000502:physiology*; D008297:Male; D015689:Oncogene Protein p21(ras) / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D004247:DNA; D015689:Oncogene Protein p21(ras)