The use of prostate specific antigen (PSA) promoter as a therapeutic target for prostate cancer

• Main Authors: Yuan-Kui Zhen, 甄原葵
• Other Authors: Chao-Liang Wu
• Format: Others
• Language: en_US
• Published: 2001
• Online Access: http://ndltd.ncl.edu.tw/handle/79899537591327369981

碩士 === 國立成功大學 === 生物化學研究所 === 89 === Abstract The development over the past decade of methods for delivering genes to mammalian cells has stimulated great interest in the possibility of treating human disease by gene-based therapies.For cancer gene therapy, the primary issue is how to express therapeutic genes specifically in cancers with the sufficient amount. Prostate-specific antigen (PSA is expressed at a high level in the luminal epithelial cells of the prostate and is absent or expressed at very low levels in other tissues. It is well known as a prostate tumor marker. Its tissue specificity renders this PSA promoter an ideal regulatory element for conferring prostate-specific transgene expression. Xanthine oxidase (XO) catalyzes the two-step oxidation of purines, such as hypoxanthine, through xanthine, to uric acid. XO may mediate anticancer activity because of its ability to generate cytotoxic reactive oxygen species (ROS), including superoxide anion radical and hydrogen peroxide.In this study, we exploited XO as the therapeutic gene to kill cancer cells, such as LNCaP (PSA-positive prostate cancer cell), PC-3 (PSA-negative prostate cancer cell) and MCF-7 (PSA-trace-expression breast cancer cell) cell lines. We constructed replication-defective AAV and adenovirus carrying the XO gene driven by the PSA promoter, and aimed to test the feasibility ofusing PSA promoter to drive XO expression in PSA-secreting cancercells, leading to cell death. To assess this viral production system, we produced EGFP-trackable viruses. The EGFP gene was detectable by PCR, indicatingthat the EGFP transgene was present in recombinant AAV.The results showed that the recombinant viruses expressing XO suppressed the growth of LNCaP cells, but had no effect on PC-3 cells. In conclusion, the PSA promoter with the XO gene may be an effective approach for the treatment of prostate cancer.