Poly(A+)RNA levels of growth-, differentiation- and transformation-associated genes in the progressive development of hepatocellular carcinoma in the rat.

Abstract

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.

• Authors: B E Huber, C A Heilman, S S Thorgeirsson
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 9 Issue 5 Pg. 756-62 (May 1989) ISSN: 0270-9139 [Print] United States
• PMID: 2468594 (Publication Type: Journal Article)

Chemical References

• Asialoglycoprotein Receptor
• DNA Probes
• RNA, Messenger
• RNA, Neoplasm
• Receptors, Immunologic
• Poly A
• RNA

Topics

• Animals
• Asialoglycoprotein Receptor
• Blotting, Northern
• DNA Probes
• Gene Expression Regulation
• Liver Neoplasms, Experimental (genetics)
• Male
• Oncogenes
• Poly A (isolation & purification)
• Precancerous Conditions (genetics)
• Proto-Oncogenes
• RNA (isolation & purification)
• RNA, Messenger
• RNA, Neoplasm (isolation & purification)
• Rats
• Receptors, Immunologic (genetics)
• Transcription, Genetic