Possible involvement of c-myc but not ras genes in hepatocellular carcinomas developing after spontaneous hepatitis in LEC rats.
LEC (Long-Evans with a cinnamon-like coat color) rats develop hepatocellular carcinomas (HCCs) spontaneously. We examined mutations of codons 12, 13, and 61 of the Ha-ras, Ki-ras, and N-ras genes in four HCCs by the polymerase chain reaction (PCR)-single-stranded DNA direct sequencing method. No ras gene mutations were observed, suggesting that ras activation is not involved in spontaneous hepatocarcinogenesis in LEC rats. The expression of mRNAs for c-myc, Ha-ras, c-raf, and the protein phosphatase 2A alpha gene (PP-2A alpha) was also examined in the four HCCs by northern blot analysis. Three of the four HCCs had c-myc expression levels approximately 30-fold higher than that in the liver of control Long-Evans rats with an agouti coat color (LEA), a sibling line of LEC rats, while the remaining HCC had an expression level sevenfold higher than that of control. In contrast, the expression levels of the Ha-ras, c-raf, and PP-2A alpha genes were the same as those in the livers of control rats. Studies of c-myc expression and mitotic index in five other HCCs, two hyperplastic nodules, and two nontumorous portions of livers of HCC-bearing LEC rats that had chronic-phase hepatitis suggested that the high level of c-myc gene expression was not due only to increased cell proliferation but might possibly be more integrally involved in hepatocarcinogenesis.
Fujimoto
Y
Y
Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan.
Ishizaka
Y
Y
Tahira
T
T
Sone
H
H
Takahashi
H
H
Enomoto
K
K
Mori
M
M
Sugimura
T
T
Nagao
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D003062:Codon; D004277:DNA, Single-Stranded / Q000235:genetics / Q000302:isolation & purification; D016259:Genes, myc; D011905:Genes, ras; D006520:Hepatitis, Animal / Q000235:genetics* / Q000473:pathology; D008099:Liver / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D008940:Mitotic Index; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains
D003062:Codon; D004277:DNA, Single-Stranded; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D012313:RNA