A lack of direct role of hepatitis B virus in the activation of ras and c-myc oncogenes in human hepatocellular carcinogenesis.
This study was performed to determine the relationship of the activation of ras and c-myc oncogenes in human hepatocellular carcinoma to the hepatitis B virus gene expression or the presence of hepatitis B virus DNA/RNA at the cellular level. This was done using immunocytochemical analysis with two different antibodies on serial sections. In addition, immunocytochemical assay for the detection of ras p21 or c-myc protein was performed in combination with in situ hybridization for hepatitis B virus DNA/RNA using 35S-labeled hepatitis B virus DNA as a probe. Investigation of a total of 14 paired human hepatocellular carcinoma and adjacent nontumorous hepatic tissues revealed enhanced expression of ras p21 in one human hepatocellular carcinoma whereas c-myc protein was found in one paired human hepatocellular carcinoma and nontumorous tissue of the same patient. Only a small proportion of human hepatocellular carcinoma cells or hepatocytes among a large number of cells on a given section showed enhanced expression, and the distribution of the oncogene product-expressing cells was focal. However, the cells overexpressing these oncogenes did not show hepatitis B surface antigen in the serial sections. Furthermore, the combined immunocytochemical and in situ hybridization assays revealed that human hepatocellular carcinoma cells overexpressing ras p21 did not show hepatitis B virus DNA/RNA, whereas some human hepatocellular carcinoma cells and nontumorous hepatocytes located away from the foci of oncogene-expressing cells gave positive signals. These findings suggest that continued expression of HBsAg or the presence of hepatitis B virus DNA/RNA in a given human hepatocellular carcinoma cell id not necessary for enhanced expression of ras or c-myc proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
Lee
H S
HS
Department of Laboratory Medicine, University of California, San Francisco 94143.
Rajagopalan
M S
MS
Vyas
G N
GN
D006528:Carcinoma, Hepatocellular / Q000032:analysis / Q000209:etiology* / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005784:Gene Amplification; D005786:Gene Expression Regulation; D011905:Genes, ras; D006514:Hepatitis B Surface Antigens / Q000032:analysis / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000032:analysis; D008113:Liver Neoplasms / Q000032:analysis / Q000209:etiology* / Q000235:genetics; D009693:Nucleic Acid Hybridization; D009856:Oncogene Proteins, Viral / Q000032:analysis; D009857:Oncogenes; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D009856:Oncogene Proteins, Viral; D012367:RNA, Viral