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 transcripts, K-ras4A and K-ras4B, which possess 2 alternative fourth coding exons. In the present study, expression of K-ras4A and K-ras4B transcripts in 8 organs, including heart, brain, spleen, lung, liver, skeletal muscle, kidney, and testis, from BALB/c mice were determined by Northern blot hybridization. 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 kidney. In addition, K-ras expression in lungs and K-ras4A/K-ras4B ratios in lung, liver, spleen, and kidney from A/J, BALB/c, C3H/HeJ, and C57BL/6J mice were 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 intermediate. Higher percentages of K-ras4A mRNA were found in lungs and kidneys from A/J and BALB/c mice, as compared with those from C3H/HeJ and C57BL/6J mice. Levels of K-ras4A and K-ras4B mRNAs were also examined in 20 NIH 3T3 cell 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 nontransformed NIH 3T3 cells and in C10 cell lines. These results suggest that: (1) there 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 from different strains of mice correlate with susceptibility to tumor induction.
Wang
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Medical College of Ohio, Toledo, Ohio, USA.
You
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M
Wang
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D016475:3T3 Cells; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D011905:Genes, ras; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D014018:Tissue Distribution
D017931:DNA Primers; D012333:RNA, Messenger