Abstract 51: Elevated levels of E2F1, EZH2 and SUZ12 lead to invasive progression of superficial bladder cancers

Abstract

Abstract Bladder cancer is increasing a rate of occurrence in aging societies. A superficial bladder cancer is noninvasive that is presented as a good prognosis after receiving treatment. However, about 20∼50% of superficial bladder cancer patients progressed to invasive tumor which represent the poor survival rates within 5 years. In previous study, we addressed if the transcriptional characteristics of the superficial bladder cancer could be used as predictive biomarkers for the progression of superficial tumors to invasive ones. Using gene expression data from 165 bladder cancer patients, we identified a gene expression signature that could predict the likelihood of progression to invasive 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. In this study, we investigated how these genes may affect the invasive and metastatic progression of superficial tumors. For confirmation of the expression of E2F1, EZH2 and SUZ12 in two groups of bladder cancer cells, we performed quantitative RT-PCR and western blot assay. Both of mRNA and protein expression of E2F1, EZH2 and SUZ12 in superficial bladder cancer were significantly lower than invasive bladder cancer cells (p< 0.0001). Next, we performed an invasion and migration assay. The overexpression of E2F1, EZH2 and SUZ12 presented an increase of invasiveness and migratory in UC9 superficial bladder cancer. On the other hand, the silencing of gene expression in EJ invasive cell was shown a significantly decreasing of invasiveness and migratory ability. Also, we determine the effect of proliferation and colony formation in superficial and invasive bladder cancer. The depletion of E2F1, EZH2 and SUZ12 in EJ and 5637 invasive bladder cancer cells that significantly decreasing of forming colonies on soft agar. Furthermore, we founded the reduction of tumor size when injected cells depleted E2F1, EZH2 and SUZ12 than control by xenograft assay. Together, our findings reveal that the estimating the roles of E2F1, EZH2 and SUZ12 for the invasive and metastatic progression in superficial bladder cancer. Citation Format: Se-Ra Lee, Yun-Gil Roh, Won-Tae Kim, Seon-Kyu Kim, Jeonghoon Heo, In-Sun Chu, Sun-Hee Leem. Elevated levels of E2F1, EZH2 and SUZ12 lead to invasive progression of superficial bladder cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 51. doi:10.1158/1538-7445.AM2014-51