Abstract B52: Identification of genes involved in early stage bladder cancer progression.

B52

Transitional cell carcinoma of the bladder (TCC) ranks 4th in incidence of all cancers in the developed world, yet the mechanisms of its origin and progression remain poorly understood. There are also few useful diagnostic or prognostic biomarkers for this disease. We have combined a transgenic mouse model for invasive bladder cancer (UPII-SV40T mice) with DNA microarray technology, in order to determine molecular mechanisms involved in early TCC development and to identify new biomarkers for detection, diagnosis and prognosis of TCC. We have identified genes that are differentially expressed between the bladders of UPII-SV40T mice and their age-matched wild type (WT) littermates at 3, 6, 20 and 30 weeks of age. These are times which correspond to premalignant, carcinoma in-situ, and early and later stage papillary TCC, respectively. There were approximately 1,900 unique genes differentially expressed (≥ 3-fold difference at one or more time points) between WT and UPII-SV40T urothelium during the time course of tumor development. Among these, there were a high proportion of cell cycle regulatory genes and cytokinesis genes that are more strongly expressed in the UPII-SV40T bladder urothelium. We have tested several of the genes upregulated in UPII-SV40T urothelium, including autocrine motility factor (AMFR), Caspase 3, Cox-2, PCNA and others as biomarkers for premalignancy in urine samples from a completed chemoprevention trial. These results will be discussed in the context of the UPII-SV40T model.

Citation Information: Cancer Prev Res 2008;1(7 Suppl):B52.