Poly(A+)RNA levels of growth-, differentiation- and transformation-associated genes in the progressive development of hepatocellular carcinoma in the rat.
The development of chemically induced hepatocellular carcinoma in the rat proceeds through a series of premalignant changes that may ultimately progress to a primary malignant tumor. Using the selection technique based on diminished binding of preneoplastic hepatocytes to tissue culture plates precoated with asialofetuin, we have isolated poly(A+)RNA from early preneoplastic foci as well as preneoplastic persistent nodules and primary hepatocellular carcinoma induced by the Solt-Farber protocol in the Fischer rat. The steady-state poly(A+)RNA levels of genes traditionally associated with growth, differentiation and/or transformation were then determined to address the question of their temporal expression in the multistep nature of cancer development. Ornithine decarboxylase- and P53-specific transcripts did not significantly change in preneoplastic foci but were increased in later-stage preneoplastic nodules and hepatocellular carcinoma. Albumin-specific transcripts were decreased in all hepatocellular carcinoma but there was no consistent coordinated increase in alpha-fetoprotein-specific transcripts. c-myc and raf transcripts increased at the very early preneoplastic foci stage and continued to increase throughout the neoplastic process. No L-myc or N-myc transcripts could be detected in any RNA sample. c-Ha-ras-specific transcripts were essentially unaltered in all RNA samples whereas no c-Ki-ras or N-ras transcripts could be detected throughout the neoplastic process. In addition, no dominant-acting transforming mutations in the ras gene family were detected by DNA transfection experiments using NIH/3T3 cells.
Huber
B E
BE
Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892.
Heilman
C A
CA
Thorgeirsson
S S
SS
D000818:Animals; D037263:Asialoglycoprotein Receptor; D015152:Blotting, Northern; D015342:DNA Probes; D005786:Gene Expression Regulation; D008114:Liver Neoplasms, Experimental / Q000235:genetics*; D008297:Male; D009857:Oncogenes; D011061:Poly A / Q000302:isolation & purification*; D011230:Precancerous Conditions / Q000235:genetics*; D011519:Proto-Oncogenes; D012313:RNA / Q000302:isolation & purification*; D012333:RNA, Messenger; D012334:RNA, Neoplasm / Q000302:isolation & purification*; D051381:Rats; D011971:Receptors, Immunologic / Q000235:genetics; D014158:Transcription, Genetic
D037263:Asialoglycoprotein Receptor; D015342:DNA Probes; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011971:Receptors, Immunologic; D011061:Poly A; D012313:RNA