BLADDER CANCER-ASSOCIATED NUCLEAR MATRIX PROTEINS

The early diagnosis of bladder cancer is central to the effective trea tment of the disease, presently, there are no methods available to eas ily and specifically identify the presence of bladder cancer cells, Th e prevailing method for the detection of bladder cancer is the identif ication of bladder cancer cells by morphological examination of exfoli ated cells or biopsy material by a pathologist. A hallmark of the mali gnant or transformed phenotype is an abnormal nuclear shape, the prese nce of multiple nucleoli, and altered patterns of chromatin organizati on, Nuclear structural alterations are so prevalent in cancer cells th at they are commonly used as markers of transformation for manly types of cancer, Nuclear shape is determined by the nuclear matrix, the dyn amic skeleton of the nucleus, The nuclear matrix is the structural com ponent of the nucleus that determines nuclear morphology, organizes th e DNA in a three-dimensional fashion that is tissue specific, and has a central role in the regulation of a number of nuclear processes, inc luding the regulation of DNA replication and gene expression, Previous investigations into prostate and breast cancer have revealed that nuc lear matrix protein (NMP) composition undergoes alterations with trans formation and that the nuclear matrix can serve as a marker for the ma lignant phenotype, In this study, we have identified NMPs with which i t is possible to differentiate human bladder tumors from normal bladde r epithelial cells, We examined the NMP composition of 17 matched tumo r and normal samples from patients undergoing surgery for bladder canc er, We have identified six proteins present in all tumor samples that are not present in the corresponding normal samples and three proteins that are unique to the normal bladder tissues in comparison with the tumor samples, Five of the six bladder cancer-associated proteins were also identified in three human bladder cancer cell lines examined (25 3j, UMUC-2, and T24), Therefore, we have demonstrated that nuclear mat rix composition is able to differentiate bladder cancer from normal bl adder tissue and may provide useful tools for early detection and recu rrence of the disease, Importantly, these markers may provide valuable tools for cytopathological screening for bladder carcinoma.