Development of a new plasmid vector with PSA-promoter and enhancer expressing tissue-specificity in prostate carcinoma cell lines.
Differential expression of the desired gene product in the target tissue is central to the concept of gene therapy. One approach is to use a tissue-specific promoter to drive therapeutic genes, such as the p53 tumor suppressor gene. To determine the feasibility of tissue-specific gene therapy for prostate cancer using prostate specific antigen (PSA) promoter and/or enhancer, in this study, we developed a tissue specific expression vector using a PSA promoter and enhancer. Our results showed that the cloned PSA promoter actively drives gene expression in the PSA-producing prostate cancer cell line (LNCaP). However, barely any promoter activity was detected in the non-PSA producing prostate cancer cell lines (DU145, PC-3) or the non-prostate cell lines (HEK-293, SAOS-2). The wild-type p53 gene driven by this PSA-promoter efficiently suppressed the growth of LNCaP. Moreover, p53 driven by the PSA enhancer-promoter cassette more efficiently suppressed the growth of the PSA-producing prostate cancer cell line (LNCaP) in vitro. This suggest that we were able to manage the tissue specificity by PSA enhancer and promoter. Additionally, the juxtaposed enhancer-promoter cassette showed great enhancement of p53 expression and apoptosis in vitro. Taken together, these results show that PSA enhancer-promoter may be a potential tool for gene therapy for prostate cancer.
Lee
S E
SE
Department of Urology, Seoul National University College of Medicine, Korea. urology@plaza.snu.ac.kr
Jin
R J
RJ
Lee
S G
SG
Yoon
S J
SJ
Park
M S
MS
Heo
D S
DS
Choi
H
H
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D000951:Antigens, Neoplasm / Q000235:genetics*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D008297:Male; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D017430:Prostate-Specific Antigen / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D000951:Antigens, Neoplasm; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D017430:Prostate-Specific Antigen; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases