Faculty Collaboration Database

Allele-specific activation and expression of the K-ras gene in hybrid mouse lung tumors induced by chemical carcinogens. Carcinogenesis 1994 Sep;15(9):2031-5

Date

09/01/1994

Pubmed ID

7923598

DOI

10.1093/carcin/15.9.2031

Scopus ID

2-s2.0-0028059022 (requires institutional sign-in at Scopus site)   44 Citations

Abstract

A mouse hybrid, (C3H x A/J)F1 or C3A, was developed by crossing male A/J mice (high lung tumor susceptibility) with female C3H mice (low lung tumor susceptibility). The lung tumor responses of the C3A mice to dimethylnitrosamine (DMN) or benzo[a]pyrene (B[a]P) were found to be intermediate between those of the two parental strains. Mutational activation of the K-ras gene was found at a high frequency in both the B[a]P- and DMN-induced C3A lung tumors. To explore the genetic basis of the K-ras gene involvement in mouse lung tumor susceptibility, the parental origin of the K-ras oncogene in the chemically induced C3A lung tumors was determined. K-ras oncogenes were found on the allele inherited from the susceptible A/J parent in 14/16 of DMN-induced tumors and 15/17 of B[a]P-induced tumors from C3A mice. Furthermore, the K-ras mRNA transcribed from the A/J allele was 5-20 times more than C3H K-ras transcripts in 10/10 DMN-induced and 10/10 B[a]P-induced C3A lung tumors. These data suggest that an activated A/J K-ras allele could be more tumorigenic than an activated C3H allele due to the differential expression of the two alleles in lung cells.

Author List

Chen B, You L, Wang Y, Stoner GD, You M

MESH terms used to index this publication - Major topics in bold

Alleles
Animals
Cocarcinogenesis
Dimethylnitrosamine
Female
Gene Expression Regulation, Neoplastic
Genes, ras
Lung Neoplasms
Male
Mice
Mice, Inbred A
Mice, Inbred C3H
Mutation
Polymerase Chain Reaction
Polymorphism, Single-Stranded Conformational