Figure 8. Pirh2 Is a Tumor Suppressor That Collaborates with p53 in Suppressing Cancer.

(A) Kaplan-Meier analysis representing the percent survival versus age in days of Wt (n = 30), Pirh2^−/− (n = 25), p53^−/− (n = 10) and Pirh2^−/− p53^−/− (n = 35) cohort of mice. (B) Tumor spectrum of p53^−/− and Pirh2^−/− p53^−/− mice. Log-rank test, P<0.0001 between Pirh2^−/− p53^−/− mice and Pirh2^−/− or p53^−/− controls. (C) Pirh2^+/−italic> mammary adenocarcinoma (H&E stain; Bar = 100 µm). This tumor is composed of a sheet of pleomorphic epithelial cells with moderate mitotic index, good vascularization and some infiltrating acute inflammatory cells. (D) Pirh2^−/− sarcoma (H&E stain; Bar = 100 µm). This tumor is composed of arrays of fusiform cells, some of them anaplastic; the tumor also shows good vascularity and some lymphocytic infiltration. (E) Pirh2^−/− p53^−/− mammary adenocarcinoma (H&E stain; Bar = 500 µm). In contrast with panel C, this tumor is a well-differentiated adenocarcinoma in which acinar structures can be seen interspersed with islets of invasive cells. (F) Pirh2^−/− p53^−/− angiosarcomas (H&E stain; Bar = 100 µm). This tumor is mostly constituted by malignant endothelial cells forming irregular spaces filled with red blood cells. (G) Immunoblot analysis showing elevated level of c-Myc in spleen from 6 week-old Pirh2^−/− p53^−/− mice compared to Wt and p53^−/− controls. (H) Immunoblot analysis showing elevated level of c-Myc in Pirh2^−/− mammary glands from 6 to 8 week-old mice and in Pirh2^−/− mammary tumors. (I) Immunoblot analysis of the level of c-Myc and p19^ARF in Wt spleen and tumors from Pirh2^−/− mice. 1: sarcoma, 2–6: lung tumors, 7: liver tumor and 8: Breast Tumor tumor. (J) Immunoblot analysis of c-Myc level in testes from 6 week-old Wt, Pirh2^−/−, and Pirh2^−/− p53^−/− mice and in Pirh2^−/− p53^−/− tumors.