Gene Therapy for Prostate Cancer Radiosensitization Using Mutant Poly (ADP-Ribose) Polymerase
Abstract
The central objective of this proposal is to express the DNA-binding domain of poly(ADP-ribose) polymerase (PARP) under control of prostate tissue-specific promoter in prostate cancer cells and sensitize them to radiotherapy or chemotherapy. Here we describe the strategy for cloning the 5-regulatory elements (1.3 kb enhancer and 0.6 kb promoter) of the human gene for prostate specific antigen (PSA). Further, we developed the recombinant plasmids that contain cDNA encoding for DNA-binding domain of PARP (PARP-DBD) downstream of the human cytomegalovirus (CMV) promoter, pCMV-DBD/F, or PSA promoter/enhancer, pPSA(EP)-DBD/F. These plasmids allow expression of the PARP-DBD protein in prostate carcinoma cells both, in constitutive and in androgen-inducible fashion. The pCMV-DBD/F construct was assayed for its ability to direct synthesis of appropriately sized FLAG-fusion protein in LNCaP prostate carcinoma cells. The availability of tissue-specific expression vectors expressing pro-apoptotic protein (PARP-DBD) offers a feasible approach for prostate cancer gene therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2001
- Accession Number
- ADA392306
Entities
People
- Viatcheslav A. Soldatenkov
Organizations
- Georgetown University