To Explore Carcinogenesis and Biological Mechanisms of Bladder Cancer (I)

Transitional cell carcinoma of the bladder is the second most common malignancy of the genitourinary tract and the second most common cause of death from genitourinary tumors. The major problem with bladder cancers is the high recurrence rate of superficial cancers: more than half of superficial tumors recur within 5 years and 10-20% progress to invasive disease. It is thus important to detect the early events in the recurrence of superficial cancer before the cancer cells have time to change their behavior to be invasive. Most of recent research in the field of bladder cancer has been focused on the identification of oncogenes and tumor suppressor genes. The order in which the genetic changes take place is important in determining the outcome of the lesion. Important difference between cancer and normal cells is hyperactivity and pleomorphism of the nucleoli. Recent results indicate that nucleolus is a site critical to cellular aging. Regulation of nucleophosmin/B23 is associated with cellular differentiation and apoptosis. Blockage of nucleophomin/B23 expression has shown that nucleophosmin/B23 is crucial for making cells resistant to such growth control. An excess of nucleophosmin/B23 is an important cause of cancer and not just a consequence. Nucleophosmin/B23 through interacting with transcription factor or tumor suppressor gene (eg. IRF-1, PCNA, YYI or p53) plays an important role in control of cellular susceptibility to growth control. Our objective is to reveal and identify proteins that play important roles in bladder carcinogenesis. Our specific aims are: 1. To characterize differential protein & mRNA expressions in bladder cancer cell lines (early & late stages) & clinical tumor tissues (primary, recurrent, various grades & stages). Their possible correlation with tumor status and prognosis of cancers will be elucidated, which could be useful in the effective management of this cancer. 2. To elucidate the regulation of proteins including nucleophosmin/B23 that are differentially-expressed and importantly associated with bladder carcinogenesis. 3. To carry out analysis of protein post-translational modifications (including those of nucleophosmin/B23) by LC/MS and to elucidate their biological roles in cell cycle, induction of apoptosis and regulation of transcriptional factors.

Project ID:PA9308-2118
External Project ID:NSC93-2745-B182-002-URD