Expression of c-Ki-ras, c-Ha-ras, and c-myc in specific cell types during hepatocarcinogenesis.
We examined the expression of six proto-oncogenes in (i) whole rat liver and isolated liver cell populations during the course of hepatocarcinogenesis induced by a choline-deficient diet containing 0.1% ethionine and (ii) fetal rat liver at different stages of development. The abundance of c-Ki-ras, c-Ha-ras, and c-myc transcripts in polysomal polyadenylated RNA from liver cells increased by 2 weeks after the start of the carcinogenic diet. c-Ki-ras and c-myc expression remained elevated during the 35 weeks of the diet, whereas c-Ha-ras transcripts increased transiently. A primary tumor sampled at 35 weeks after the carcinogenic diet was started contained high levels of both c-Ki-ras and c-myc RNA. The abundance of c-src transcripts was unchanged throughout carcinogenesis; c-abl and c-mos transcripts were not detected in either preneoplastic or neoplastic livers. To determine which cell types within the liver contained proto-oncogene transcripts, we isolated hepatocytes, oval cells, and bile duct cells from normal and preneoplastic livers. The results indicate that proto-oncogenes are expressed differentially in these cell types during hepatocarcinogenesis and that the expression of c-Ki-ras and c-myc is high in oval cells throughout carcinogenesis. In developing livers, c-Ki-ras, c-Ha-ras, and c-myc transcript levels were high at 17 days of gestation but reached the low values characteristic of adult rat livers between 20 days of gestation and 3 days after birth.
Yaswen
P
P
Goyette
M
M
Shank
P R
PR
Fausto
N
N
D000818:Animals; D005786:Gene Expression Regulation; D008099:Liver / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D008114:Liver Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D008297:Male; D009857:Oncogenes; D011230:Precancerous Conditions / Q000235:genetics*; D012313:RNA / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D014158:Transcription, Genetic
D012333:RNA, Messenger; D012313:RNA