Figure 2. Arf attenuates response to cisplatin in a GEM model of MIBC.

(A–E) Experimental design. Arf-wild-type (Arf^+/+; p53^f/f; Pten^f/f) or Arf-null (Arf^f/f; p53^f/f; Pten^f/f) mice were induced to form tumors by delivery of adeno-Cre into the bladder lumen and monitored by ultrasound imaging. Mice were treated with vehicle of cisplatin (2 mg/kg) when tumors reached 1 mm and continued for up to 2 months. (A) Representative images showing whole mount tumors, ultrasound images, H&E staining, or immunostaining with the indicated markers. The numbers in the ultrasound images show the tumor volume; scale bars represent 50 microns; Insets show high power views. (B) Summary of weekly monitoring of tumor volume measured by ultrasound imaging; p-values were calculated using an ANOVA test. (C) Summary of tumor weights for the indicated groups. n=9–15/group (see Table S1B); p-values were calculated using a Mann Whitney U test. (D) Quantification of cellular proliferation as assessed by Ki67 staining of tumor cells. (E) Uptake of Pt-GG in the indicated tumor types. In D and E, n=3/group; p-values were calculated using a Mann Whitney U test.

See also Figure S1 for additional details of the mouse phenotype, and Table S1 for details regarding the mouse cohorts and preclinical studies.