Faculty Collaboration Database

The second intron of the K-ras gene contains regulatory elements associated with mouse lung tumor susceptibility. Proc Natl Acad Sci U S A 1994 Feb 15;91(4):1589-93

Date

02/15/1994

Pubmed ID

8108449

Pubmed Central ID

PMC43205

DOI

10.1073/pnas.91.4.1589

Scopus ID

2-s2.0-0027979481 (requires institutional sign-in at Scopus site)   89 Citations

Abstract

We have previously demonstrated the preferential activation of the K-ras gene from the susceptible A/J parent in lung tumors from F1 mouse hybrids. In the present study, the mechanism of this observation is further investigated. Higher levels of expression of A/J K-ras allele were detected in lung adenomas (30 of 30) from the C3A mouse. In addition, three K-ras alleles, designated as susceptible (Ks), intermediate (Ki), or resistant (Kr), were identified by sequence analysis of the second intron of the K-ras gene from 32 strains of mice. These K-ras alleles are associated with differences in mouse lung tumor susceptibility. All Kr alleles have a tandem 37-bp direct repeat (nt 282-355) in the second intron of the K-ras gene. Ks and Ki alleles have only one copy of the 37-bp sequence (nt 282-318). Ks strains have three base variations at nt 288, 296, and 494, and Ki strains have two base variations at nt 288 and 494 in the second intron of the K-ras gene. Differential protein-binding patterns were observed in gel-mobility-shift experiments between the duplicated 37-bp sequence of the Kr allele and the single 37-bp sequence of the Ks and Ki alleles. DNase I footprinting assay revealed protein binding sites in the second intron of the K-ras gene that correspond to the tandem repeat sequences. Our data suggest that higher expression of the A/J allele relative to C3H allele may be responsible for the allele-specific activation of the K-ras gene in lung tumors from F1 hybrid mice.

Author List

Chen B, Johanson L, Wiest JS, Anderson MW, You M

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

Adenoma
Alleles
Animals
DNA, Neoplasm
Gene Expression Regulation, Neoplastic
Genes, ras
Genetic Predisposition to Disease
Genetic Variation
Genotype
Introns
Lung Neoplasms
Mice
Mice, Inbred Strains
Nuclear Proteins
Protein Binding
Regulatory Sequences, Nucleic Acid
Repetitive Sequences, Nucleic Acid
Sequence Analysis, DNA
Species Specificity