1. DEVELOPMENT OF PROSTATE-SPECIFIC ANTIGEN PROMOTER-BASED GENE THERAPY FOR ANDROGEN-INDEPENDENT HUMAN PROSTATE CANCER
- Author
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Akinobu Gotoh, Jan Trapman, Chinghai Kao, Leland W. K. Chung, Tadayuki Miyamoto, Jun Cheon, Toshiro Shirakawa, Ling-Jun Ho, Song Chu Ko, Thomas A. Gardner, Catharina B.J. Cleutjens, and Frank L. Graham
- Subjects
medicine.medical_specialty ,business.industry ,Genetic enhancement ,Urology ,Cancer ,Promoter ,urologic and male genital diseases ,medicine.disease ,Prostate-specific antigen ,Prostate cancer ,medicine.anatomical_structure ,Endocrinology ,Prostate ,Thymidine kinase ,Internal medicine ,LNCaP ,medicine ,Cancer research ,business - 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...
- Published
- 1998
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