Development of prostate-specific antigen promoter-based gene therapy for androgen-independent human prostate cancer
- Authors
- Gotoh A.; Ko S.-C.; Shirakawa T.; Cheon J.; Kao C.; Miyamoto T.; Gardner T.A.; Ho L.-J.; Cleutjens C.B.J.; Trapman J.; Graham F.L.; Chung L.W.K.
- Issue Date
- 1998
- Publisher
- Lippincott Williams and Wilkins
- Keywords
- Androgen; Gene therapy; Hormonal refractory cancer; Prostate cancer; PSA; Tissue specific promoter
- Citation
- Journal of Urology, v.160, no.1, pp 220 - 229
- Pages
- 10
- Indexed
- SCOPUS
- Journal Title
- Journal of Urology
- Volume
- 160
- Number
- 1
- Start Page
- 220
- End Page
- 229
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/25020
- DOI
- 10.1016/S0022-5347(01)63094-5
- ISSN
- 0022-5347
1527-3792
- Abstract
- Purpose: The goal of this study is to develop a tissue-specific toxic gene therapy utilizing the prostate specific antigen (PSA) promoter for both androgen-dependent (AD) and androgen-independent (AI) PSA-secreting prostate cancer cells. Ideally this gene therapy would be effective without the necessity of exposing the target cells to circulating androgens. Materials and Methods: An AI subline of LNCaP, an AD PSA-secreting human prostate cancer cell line, C4-2, was used in this study. Castrated mice bearing C4-2 tumors secrete PSA. A transient expression experiment was used to analyze the activity of two PSA promoters, a 5837 bp long PSA promoter and a 642 bp short PSA promoter, in C4-2 cells. A recombinant adenovirus (Ad-PSA-TK) carrying thymidine kinase under control of the long PSA promoter was generated. The tissue-specific activity of Ad-PSA-TK was tested in vitro and in vivo. Results: The long PSA promoter had superior activity over short PSA promoter, and higher activity in C4-2 cells than in LNCaP cells. High activity of Ad- PSA-TK was observed in C4-2 cells in an androgen deprived condition. In vitro, Ad-PSA-TK was further demonstrated to induce marked C4-2 cell-kill by acyclovir in medium containing 5% FBS. No cell-kill was observed in control WH cells (a human bladder cancer cell line). In vivo, Ad-PSA-P-TK with acyclovir significantly inhibited subcutaneous C4-2 tumor growth and PSA production in castrated animals. Conclusion: The 5837 bp long PSA promoter was active in the androgen free environment and could be used to target both androgen-dependent and independent PSA-producing prostate cancer cells in vitro, and prostate tumors in castrated hosts.
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- Appears in
Collections - 2. Clinical Science > Department of Urology > 1. Journal Articles
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