Characterization of tumor cell lines derived from genetically engineered mouse models of bladder cancer

We have generated various genetically engineered mouse models (GEMMs) of advanced bladder cancer that recapitulate various morphological variants of human tumors, with distinct histological characteristics, differing onset times or growth rates, and varying incidences of dissemination. To investigate the molecular pathways underlying these features, we performed a transcriptomic analysis of these models in comparison with control urothelium. Given that concurrent TP53 and RB1 alterations are frequently observed in human tumors and are associated with specific molecular subtypes and increased aggressiveness, this study aimed to develop and characterize new models comparing the combined loss of Pten, Trp53, and Rb1 (in an Rbl1-null background, due to functional compensation of Rb1 loss in mouse tissues) with the loss of Pten and Trp53 alone, where the retinoblastoma (Rb) family remains intact. In both models, basal urothelial cells were targeted using adenoviruses expressing Cre unther de control of the Krt5 promoter (Ad5-Krt5-Cre), while luminal urothelial cells were targeted using the murine Krt20 promoter (Ad5-Krt20-Cre). Despite the advantages offered by these GEMMs, their limitations—including unpredictable tumor onset, long latency periods, and difficulties in early tumor detection—led us to develop immunocompetent heterotopic models using tumor cell lines derived from primary tumors arising in GEMMs. These models enable more accurate tumor monitoring and synchronized growth, thereby improving the robustness of preclinical studies. Here, we provide a transcriptomic analysis of some of these bladder tumor-derived cells.