PROSTATE-SPECIFIC AMPLIFICATION OF EXPANDED POLYGLUTAMINE EXPRESSION - A NOVEL-APPROACH FOR CANCER GENE-THERAPY

For cancer gene therapy, it is of primary importance to develop a syst em to sufficiently and selectively express therapeutic genes in cancer cells. In this study, we showed that an approximately 5.3-kb promoter region of the prostate-specific antigen (PSA) gene can replicate the endogenous expression pattern, although its expression is very weak, W e then developed a novel two-step transcriptional activation system in which the PSA promoter drives an artificial transcriptional activator , GAL4-VP16 fusion protein, and it in turn activates transgene express ions under the control of GAL4-responsive elements. By using this syst em, transgene expressions can be greatly augmented while maintaining p rostate-specific expression, Finally, we applied this system to drive an expanded polyglutamine, a potent proapoptotic molecule, to induce a poptosis selectively in PSA-positive prostate cancer cells. This novel system would provide an ideal approach for cancer gene therapy applic able not only to prostate cancer but to other cancers as well.