ANALYSIS OF MAP-KINASE IN THE BLADDER CANCER AND TARGETED MOLECULAR STRATEGIES BASED ON THE BLOCKADE OF THE MAP-KINASE PATHWAYS

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Background: The mitogen-activated protein kinase (MAPK) cascade plays a crucial role in the transduction of extra cellular signals into responses governing growth and differentiation. The effects of a specific inhibitor of the MAPK kinase pathway on inhibition of urothelial cancer cell cycle-dependent kinases have been examined. Materials and Methods: We evaluated the expression of Elk-1 mRNA in 15 normal urine samples or 20 urine sample of the patient with bladder cancer, and 20 normal urothelial or 40 bladder cancer specimens. We investigated inhibition effect of MAPK activation in bladder cancer by studying the effect of MEK1/2 inhibitor on a panel of six human urothelial carcinoma cell lines. Results: Elk-1 mRNAexpression was not detected in any of the normal urine samples and normal urothelial mucosa. In the other, Elk-1 mRNA expressed all of the human transitional cell carcinoma cell lines, 20.0% urine sample of the patient with bladder cancer and 70.0% bladder cancer specimens. No relations were observed between the Elk-1 mRNA expression and pathological grade or staging in bladder cancer specimens. Several TUNEL positive cells were present in specimens 6 bladder cancer cells treated with MEK1/2 inhibitor. The expression level of the MAPK pathway in six bladder cancer cell lines using MAPK phosphorylation assay were various. The MEK inhibitor induced slightly apoptosis in UC cell lines by TUNEL methods, but not inhibited phosphorylation of MAPK in the MAPK Assays. Conclusions: Only MAPK phosphorylation may not contribute to carcinogenesis and tumor proliferation in the bladder cancer. As a result, activation of Elk-1 in nucleus may contribute to carcinogenic transformation rather than in tumor progression.