The Role of E2F3 in Bladder Cancer Functions
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Date
2012-06
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The Ohio State University
Abstract
Bladder cancer is one of the most expensive types of cancer to treat due to its high recurrence rate and the costly methods of its treatment. Improved mechanistic understanding of genetic changes commonly associated with bladder cancer and how the changes contribute to cancer development will lead to the identification of new therapeutic targets. These molecular targets may increase patient survival rate and decrease reoccurrence of tumors. A number of experimental studies support the role of E2F genes in regulating cell cycle progression and gene expression for a broad spectrum of biological functions. Retinoblastoma (pRB), an important tumor suppressor, is a major regulator of E2F genes, and, traditionally, inactivation of RB is sufficient to induce cell proliferation by releasing E2F3, a transcription factor involved in cell cycle progression. However, E2F3 is commonly over-expressed in high-grade and stage tumors. Our hypothesis is that co-existence of pRB inactivation and E2F3 over-expression in the same tumor implicate E2F3 as an integral protein in promoting cancer cell functions beyond cell cycle progression. Using a bladder cancer cell line which has over-expression of E2F3 and loss of pRb, we have knocked down the expression of E2F3 and analyzed the change in specific cellular functions, including proliferation and invasion. We have also developed a mouse model of bladder cancer that is representative of the human condition. We found that upon E2F3 knockdown, cellular invasion levels decreased by about 40%. Although more invasion assays are needed to confirm this data, a drop in cellular invasion upon E2F3 knockdown substantiates our original hypothesis, possibly explaining E2F3 as a major regulator in the molecular pathway of cancer cell invasion.
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Keywords
Cancer, Bladder, Molecular Biology, Biomedical