Mutational activation of the c-Ha-ras gene in liver tumors of different rodent strains: correlation with susceptibility to hepatocarcinogenesis.

Abstract

The frequency and pattern of mutations at codon 61 of the c-Ha-ras gene

Liver-targeted disruption ofApcin mice activates β-catenin signaling and leads to hepatocellular carcinomas

“…Even if in most chemically induced HCCs, mutations of ␤-catenin are exclusive of those of H-Ras (28,29), a recent study using mouse technology proposed that the forced activation of H-Ras could be the genetic event that cooperates with activated ␤-catenin to cause hepatocarcinogenesis (30). Therefore, we analyzed two micronodules and the nine HCCs identified for known hot spot mutations on codons 12-13 and codon 61 of the H-Ras gene (31). No H-Ras mutation was observed in any of these samples (data not shown).…”

Inhibition of spontaneous development of liver tumors by inoculation with dendritic cells loaded with hepatocellular carcinoma cells in C3H/HeNCRJ mice

“…35 The very high rate of spontaneous liver tumor in C3H mice has been closely associated with Ha-ras oncogene mutation at codon 61. 36 In the present study, we also addressed whether inoculation of DCs loaded with HCC cells by treatment with PEG could induce antitumor immunity to regress preexisting tumor. For this purpose, we used 13-month-old C3H/ HeNCrj mice that were suspected of having liver tumors.…”

Selective pressure during tumor promotion by phenobarbital leads to clonal outgrowth of β-catenin-mutated mouse liver tumors

“…DEN-induced mouse liver tumors frequently harbor point mutations in ras genes, particularly at codon 61 of Ha-ras (e.g. see Buchmann et al, 1991;Bauer-Hofmann et al, 1992). Ras proteins play an important role in cellular transduction pathways that mediate signals from transmembrane receptors into the nucleus.…”

“…In this experiment, PB was found to signi®cantly promote hepatocarcinogenesis in Cx32-wildtype mice . Liver tumors from Cx32-wildtype mice were now screened for the presence of mutations in Ha-ras codon 61 by allele-speci®c oligonucleotide hybridization as described recently (Buchmann et al, 1991;Bauer-Hofmann et al, 1992), and b-catenin mutations were analysed by sequencing of exon 2 which corresponds to human exon 3 (de La Coste et al, 1998). Typical examples of b-catenin mutation analyses are given in Figure 1.…”