Overexpression of cyclooxygenase-2 (COX-2) in the mouse urinary bladder induces the expression of immune and cell proliferation related genes
Advisor:Klein, Russell D.
Contributors:Colby, Jennifer K.
Fischer, Susan M.
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Series/Report no.:Interdisciplinary Ph.D. Program in Nutrition - OSUN. Graduate student poster competition, 2006
Bladder cancer is a common malignancy. Numerous studies have demonstrated that increased expression of cyclooxygenase enzyme 2 (COX-2), which catalyzes the synthesis of prostaglandins (PGs), is associated with the development and progression of certain type of cancers, including bladder cancer. However, the exact role of COX-2/PGs play in bladder carcinogenesis remains unknown. We have recently developed a transgenic mouse model which overexpresses COX-2 under the control of a bovine keratin 5 (BK5) promoter. The BK5.COX2 mice develops high incidence of bladder transitional cell hyperplasia (TCH) and a relative lower incidence of bladder papilloma. We then conducted a micorarray gene analysis to determine the effects of COX-2 overexpression on the regulation of gene expression profile in bladder carcinogenesis. Analysis of gene array data by t-test (p<0.05) revealed 70 of the upregulated genes and 60 of the downregulated genes had expression changed by 2-fold or more in transgenic compared to wild-type bladders. Gene set analysis using Expression Analysis Systematic Explorer software revealed that genes associated with Immune/Stress Response and Cell Cycle/Proliferation biologic processes were significantly overrepresented in the top 100 upregulated genes. Relevant downregulated genes included three TGF beta related genes (Tgfb2, Tgfb3, Tgfbi), and the anti-angiogenic gene thrombospondin 2 (Thbs2). We further demonstrated that the growth factor, epiregulin, is the most highly induced gene among the genes validated by real-time PCR. The results of gene expression analysis indicate that the initial response of the mouse bladder to elevated COX-2 expression includes mounting an inflammatory response and inducing cell proliferation.
CA091865 and CA100140 from the National Cancer Institute.
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