Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
Research Abstract |
A number of genetic changes have been shown to occur in prostate tumorigenesis, yet it is difficult to translate this molecular knowledge into diagnostic and prognostic criteriae widely applicable for the management and treatment of the disease. Recent molecular studies have demonstrated several candidate genes important in hereditary prostate cancer; however, no specific molecular marker for this tumor has as yet been found. In searching for potential gene markers for prostate carcinoma, we explored the molecular profile relating to the gene expression patterns in tumors using fluorescent differential display (FDD) analysis. We have identified a novel gene, designated prostate cancer antigen-1 (PCA-1), which shows increased expression in prostate carcinoma. The full-length transcript corresponding to the PCR product was cloned by rapid amplification of CDNA ends. Analysis of the deduced amino acid sequence demonstrated that this gene encodes a novel 50-Kda putative protein immunohistochemically expressed in a high number of prostate carcinomas (63/70; 90%) as well as in the atypical cells in high-grade prostatic intraepithelial neoplasias. Western blot analysis indicates that PCA-1 is also up-regulated in prostate cancer cell lines PC-3 and DU 145, but not in LNCaP Other human cancers, such as thyroid, gastric colorectal, lung, breast, and renal cell cancers, proved negative for PCA-1 , indicating specificity for prostatic lesions. Although there appears to be no significant correlation between immunoreactivity and histological tumor grade or pathological stage, the gene may be relevant to the early stages of the tumor development, thus making it useful as a diagnostic and therapeutic tool for dealing with prostate cancer.
|