Targeting suicide gene therapy for prostate cancer utilizing HVJ-liposome

点击翻译按钮获取中文摘要

For advanced stage of prostate cancers, androgen ablation is the standard choice of treatment and initially it is effective for the majority of patients. However, once cancer becomes relapsed and refractory to androgen ablation therapy, there is no clear consensus of treatments that overcome this disease. Thus, various gene therapies against prostate cancer, especially in a tissue-specific manner, are currently being widely investigated.Prostate-specific membrane antigen (PSMA) is a transmembrane protein predominantly expressed on human neoplastic prostate epithelial cells. For the development of targeting gene therapy, we are investigating a tissue-specific promoter of PSMA gene. A 1244bp DNA fragment consisted of 5'-flanking region of PSMA gene was cloned into a luciferase reporter plasmid. In PSMA producing LNCaP human prostate cancer cell line, putative PSMA promoter activity was approximately 40% of that of the SV40 promoter/enhancer and it was inversely increased with androgen depletion. While, in other non-PSMA producing prostate and non-prostate cancer cell lines, the promoter activity was not higher than 11% of its control and independent to the androgen concentration. Further evaluation with its deletion constructs revealed possible negative regulatory elements in the PSMA promoter. These unique features of the PSMA promoter in contrast to the prostate-specific antigen promoter will be potentially useful for targeting gene therapy against PSMA producing prostate cancers.