Liver hyperplasia is not necessarily associated with increased expression of c-fos and c-myc mRNA.
Experiments were designed to investigate the expression of three cell-cycle-dependent proto-oncogenes in response to two different types of proliferative stimuli: compensatory cell proliferation after partial hepatectomy (PH) or CCl4 and liver hyperplasia induced by the mitogens ethylene dibromide (EDB) and cyproterone acetate (CPA). Steady-state levels of messenger RNAs for c-fos and c-myc were found to be elevated after PH or CCl4 with a maximum increase between 0.5 and 2 h for c-fos and at 2-3 h for c-myc and a rapid decline after 3 h. However, when liver cell proliferation was induced by mitogens, no increase in the expression of c-fos mRNA was observed with both EDB or CPA during the first 24 h. In addition, elevated expression of c-myc was found only in liver hyperplasia induced by EDB, but not with CPA. While the expression of c-myc mRNA and c-fos mRNA was different in the two types of proliferative stimuli, that of c-Ha-ras and c-Ki-ras was similar in all the experimental groups. Cell proliferation monitored by means of incorporation of labelled thymidine into DNA or mitotic index at 24 h following PH, EDB and CPA occurred at a similar extent in all the experimental groups. Our data indicate that the transient and sequential expression of cell-cycle-related genes may vary in response to proliferative stimuli of different nature and suggest that increased expression of cell-cycle-related genes may not be a necessary prerequisite for the entry of the cells into the cell cycle.
Coni
P
P
Istituto di Farmacologia e Patologia Biochimica, Università di Cagliari, Italy.
Pichiri-Coni
G
G
Ledda-Columbano
G M
GM
Rao
P M
PM
Rajalakshmi
S
S
Sarma
D S
DS
Columbano
A
A
D000818:Animals; D002251:Carbon Tetrachloride; D002455:Cell Division / Q000187:drug effects; D003534:Cyproterone / Q000031:analogs & derivatives; D017373:Cyproterone Acetate; D015946:Ethylene Dibromide; D015870:Gene Expression / Q000187:drug effects*; D011905:Genes, ras / Q000235:genetics; D006498:Hepatectomy; D006965:Hyperplasia / Q000139:chemically induced / Q000235:genetics; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000473:pathology*; D008297:Male; D011519:Proto-Oncogenes / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains
D012333:RNA, Messenger; D015946:Ethylene Dibromide; D017373:Cyproterone Acetate; D002251:Carbon Tetrachloride; D003534:Cyproterone