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 4
Sequence of urothelial tumorigenesis in heterozygous and homozygous ras transgenics (A) and tumorigenesis in different parts of the urinary tract (B). (A) Urinary bladders from 1- to 6-month-old heterozygous (top row) and homozygous (bottom row) mice were assessed for histopathological changes, and representative images are shown. Whereas heterozygous mice showed simple urothelial hyperplasia with no frank tumors throughout this time period, homozygous mice showed marked hyperplasia at 1 month, nodular and papillary hyperplasia at 2–3 months, and urothelial tumors as early as 3–4 months, with significant increase in volume at 5–6 months. Original magnification, ×50. (B) The renal pelvis (arrowheads), ureter, and bladder urothelia of a 6-month-old heterozygous mouse all exhibited hyperplastic urothelial changes, while an age-matched homozygous mouse developed papillary tumors (arrows) not only in the bladder, but also in the renal pelvis and ureter. L, lumen; RP, renal papilla. Original magnification, ×200 for all panels except the lower-right panel (×50).