Figure 1

(A) Expression of one copy of mutant HRAS driven by the Upk2 promoter results in urothelial hyperplasia, while expression of two copies of mutant HRAS results in noninvasive bladder cancer (NIBC). However, because FOXA1 is a direct regulator of UPK2 in human cells20, we hypothesized that Foxa1 KO would (B) result in one of three possibilities: (1) decreased Upk promoter activity, decreased mutant HRAS expression, and regression of urothelial hyperplasia in Upk2-HRAS* mice; (2) increased proliferation and/or squamous differentiation in Upk2-HRAS* mice; or no impact/unpredictable results. (C) Western blotting of protein lysates for HRAS*, Foxa1, E-cadherin and pan-cytokeratin following bladder dissection. (C) Q-RT-PCR using probes specific for HRAS* expression. These results indicate that Foxa1 KO results in reduced expression of HRAS* in the Upk2-HRAS* mouse model.