Decreased Tumorigenesis and Mortality from Bladder Cancer in Mice Lacking Urothelial Androgen Receptor

摘要: Much fewer mice lacking androgen receptor (AR) in the entire body develop bladder cancer (BCa). However, role of urothelial AR (Uro-AR) BCa development remains unclear. In present study, we generated that lacked only Uro-AR (Uro-AR−/y) to by using carcinogen BBN [N-butyl-N-(4-hydroxybutyl)-nitrosamine] and found Uro-AR−/y had a lower incidence higher survival rate than did their wild-type (WT; Uro-AR+/y) littermates. In vitro assay also demonstrated facilitates neoplastic transformation normal cells carcinoma. IHC staining exhibited less DNA damage, with much expression p53 its downstream target protein PNCA WT urothelium, which suggests may modulate tumorigenesis through p53-PCNA repair signaling. Indeed, transgene, simian vacuolating virus 40 T (SV40T), urothelium (Uro-SV40T-AR−/y) similar as littermates (Uro-SV40T-AR+/y), was inactivated SV40T both genotypes. Use degradation enhancer ASC-J9 led suppression tumorigenesis, few adverse effects BBN-induced mouse model. Together, these results provide first direct in vivo evidence has an important promoting progression. Targeting novel approach suppress initiation.