Hyperactivation of Ha-ras oncogene, but not Ink4a/Arf deficiency, triggers bladder tumorigenesis
J. Clin. Invest. Lan Mo, et al. 117:314 doi:10.1172/JCI30062 [Go to this article.]

Figure 2
Analysis of synergism between Ha-ras activation and Ink4a/Arf deficiency. (A) Southern blot analysis of a representative transgenic mouse litter derived from intercrossing and backcrossing between UPII/Ha-ras-M transgenics and Ink4a/Arf knockouts. Upper panel: analysis of the Ink4a/Arf alleles (WT allele: 9.2-kb; KO allele: 6.0 kb). Lower panel: analysis of the UPII/Ha-ras-M allele (Tg: 1.7-kb; endogenous UPII gene [EG]: 1.4 kb). Mice of several genotypes were obtained, including mice wild-type for both genes (lane 2); mice heterozygous for the ras mutant allele alone (lane 8); mice heterozygous for the Ink4a/Arf allele alone (lanes 4 and 6); mice homozygous for the Ink4a/Arf-knockout allele alone (lane 10); mice heterozygous for the ras mutant allele and heterozygous for the Ink4a/Arf allele (lane 1); and mice heterozygous for the ras mutant and homozygous for the Ink4a/Arf-knockout allele (lanes 3, 5, 7, and 9). (B) Histopathology of urinary bladders from a wild-type mouse showing normal morphology; a ras-transgenic mouse (11 months) showing simple urothelial hyperplasia; an age-matched Ink4a/Arf-knockout mouse showing normal morphology; a mouse heterozygous for both ras mutant allele and Ink4a/Arf allele showing simple urothelial hyperplasia; and a mouse heterozygous for the ras mutant and nullizygous for the Ink4a/Arf allele also showing simple urothelial hyperplasia. Note that deficiency of Ink4a/Arf failed to accelerate ras-induced urothelial tumor formation. */WT denotes mice heterozygous for the Ha-ras mutant. Original magnification, ×200.