Stimulation of protooncogene expression by partial hepatectomy is not tissue-specific.
We have characterized the early protooncogene response and the later cell proliferative response in the kidneys and livers of normal rats cross-circulated with partially hepatectomized animals. Increase c-myc and C-Ha-ras expression was observed in the kidneys of totally hepatectomized rats, as well as those of their cross-circulated partners. This indicates that the initial response to hepatectomy is not organ-specific, although the later DNA synthetic response of the kidney is only approximately one-tenth that of regenerating liver. Expression of c-myc and c-Ha-ras is dramatically increased in the livers of both hepatectomized and nonhepatectomized, parabiotic (cross-circulated) rats within 1 hr of partial hepatectomy, confirming the presence of a circulating factor which stimulates protooncogene expression early in regeneration. DNA synthesis was also stimulated in the livers of the cross-circulated animals between 20 and 26 hr following hepatectomy, but only to a level one-eighth that of the livers of hepatectomized animals. Normal rats cross-circulated with totally hepatectomized animals also demonstrated an early increase in hepatic c-myc and c-Ha-ras expression, indicating that regeneration must be stimulated by an extrahepatic signal. Our data suggest that the early increase in protooncogene expression is a non-organ-specific response to partial hepatectomy which does not insure subsequent cellular proliferation. The organ specificity of liver regeneration must involve an event separate from the early stimulation of protooncogene expression.
Roesel
J
J
Department of Internal Medicine, University of Alabama, Birmingham.
Rigsby
D
D
Bailey
A
A
Alvarez
R
R
Sanchez
J D
JD
Campbell
V
V
Shrestha
K
K
Miller
D M
DM
D000818:Animals; D004247:DNA / Q000096:biosynthesis; D015870:Gene Expression; D006133:Growth Substances / Q000502:physiology; D006498:Hepatectomy; D008099:Liver / Q000378:metabolism*; D008115:Liver Regeneration; D009928:Organ Specificity; D011519:Proto-Oncogenes; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic
D006133:Growth Substances; D004247:DNA