Alternative splicing of the K-ras gene in mouse tissues and cell lines

The mRNA from the K-ras protooncogene is alternatively spliced into 2 trans cripts, K-ras4A and K-ras4B, which possess 2 alternative fourth coding exon s. In the present study, expression of K-ras4A and K-ras4B transcripts in 8 organs, including heart, brain, spleen, lung, liver, skeletal muscle kidne y, and testis, from BALB/c mice were determined by Northern blot hybridizat ion. k-ras4B, observed in all organs, accounted for approximately 90% to 99 % of total K-ras mRNA. K-ras4A. was detected only in lung, liver, and kidne y. In addition, K-ras expression in lungs and K-ras4A/K-ras4B ratios in lun g, liver, spleen and kidney from A/J, BALB/c, C3H/HeJ, and C57BL/6J mice we re determined. A/J lungs expressed K-ras mRNA 2-fold higher than C3H/HeJ or C57BL/6J lungs, whereas K-ras mRNA expression in BALB/c lungs was intermed iate Higher percentages of K-ras4A mRNA were found in lungs and kidneys fro m A/J and BALB/c mice, as compared with those from C3H/HeJ and C57BL/6J mic e. Levels of K-ras4A and K-ras4B mRNAs were also examined in 20 NIH 3T3 cel l lines transformed by DNA from spontaneous A/J mouse lung tumors. K-ras4A was expressed 2- to 3-fold higher in these cell lines than in nontransforme d NIH 3T3 cells and in CIO cell lines. These results suggest that: (1) ther e may be functional differences between the protein encoded by K-ras4A and that encoded by K-ras4B in each tissue type, and in tumor cells; and (2) K- ras mRNA expression and K-ras4A/K-ras4B ratios detected in lung tissues fro m different strains of mice correlate with susceptibility to tumor inductio n.