Prostate-specific amplification of expanded polyglutamine expression: a novel approach for cancer gene therapy
Segawa, T.; Takebayashi, H.; Kakehi, Y.; Yoshida, O.; Narumiya, S.; Kakizuka, A.
Cancer Research 58(11): 2282-2287
1998
ISSN/ISBN: 0008-5472 PMID: 9622059 Document Number: 485315
For cancer gene therapy, it is of primary importance to develop a system 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. We 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 expressions under the control of GAL4-responsive elements. By using this system, transgene expressions can be greatly augmented while maintaining prostate-specific expression. Finally, we applied this system to drive an expanded polyglutamine, a potent proapoptotic molecule, to induce apoptosis selectively in PSA-positive prostate cancer cells. This novel system would provide an ideal approach for cancer gene therapy applicable not only to prostate cancer but to other cancers as well.