Abstract 1994: Mediators responsible for the invasive progression of superficial bladder cancers

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Bladder cancer is seventh most prevalent type of cancer worldwide and accounts for an estimated 150,000 deaths annually. Urothelial carcinoma of the bladder accounts for more than 90% of bladder cancers. This cancer presents as a heterogeneous disease that consists of two main phenotypic groups with distinct biological behaviors and prognoses: Approximately 80% of patients have tumors that are superficial or non-muscle invasive, and the remaining 20% of tumors presents as a muscle-invasive tumor with dismal prognosis. After early treatment by surgical resection and intravesical immunotherapy, around 20% of these patients have disease progression to invasive tumors and eventually die of the disease. Current methods of predicting the clinical behavior of these tumors prospectively are unreliable. Due to the progress of superficial bladder cancer into invasive bladder cancer, a development of marker that could identify superficial cancers with a high risk of progression is needed. In our microarray analysis from 165 bladder cancer patients, supervised analysis of gene expression data revealed a gene expression signature that is strongly associated with invasive bladder tumors. Gene network analyses of the signature revealed that E2F1 and its downstream effectors EZH2 and SUZ12 could be important mediators for the invasive and metastatic progression of superficial tumors. Furthermore, we investigated how these genes may affect the invasive and metastatic progression of superficial tumors. We investigated the invasive ability by these genes in two groups of bladder cancer cell lines: One group (UC9 and UC14) has a superficial signature of bladder cancer, and the other group (EJ and UC13) has an invasive signature of bladder cancer. We examined the effects of overexpression or siRNA inhibition of these genes on cell growth, wound healing migration and invasion in bladder cancer cell lines. We will report the results estimating the roles of these genes for the invasive and metastatic progression in bladder cancer cell lines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1994.