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A novel TARP-promot...
A novel TARP-promoter-based adenovirus against hormone-dependent and hormone-refractory prostate cancer
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- Cheng, Wing-Shing (author)
- Uppsala universitet,Enheten för klinisk immunologi
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Kraaij, Robert (author)
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- Nilsson, Berith (author)
- Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi
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van der Weel, Laura (author)
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de Ridder, Corrina M.A. (author)
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- Tötterman, Thomas H. (author)
- Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi
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- Essand, Magnus (author)
- Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi
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(creator_code:org_t)
- Elsevier BV, 2004
- 2004
- English.
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In: Molecular Therapy. - : Elsevier BV. - 1525-0016 .- 1525-0024. ; 10:2, s. 355-364
- Related links:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- TARP (T cell receptor gamma-chain alternate reading frame protein) is a protein that in males is uniquely expressed in prostate epithelial cells and prostate cancer cells. We have previously shown that the transcriptional activity of a chimeric sequence comprising the TARP promoter (TARPp) and the PSA enhancer (PSAe) is strictly controlled by testosterone and highly restricted to cells of prostate origin. Here we report that a chimeric sequence comprising TARPp and the PSMA enhancer (PSMAe) is highly active in testosterone-deprived prostate cancer cells, while a regulatory sequence comprising PSAe, PSMAe, and TARPp (PPT) has high prostate-specific activity both in the presence and in the absence of testosterone. Therefore, the PPT sequence may, in a gene therapy setting, be beneficial to prostate cancer patients that have been treated with androgen withdrawal. A recombinant adenovirus vector with the PPT sequence, shielded from interfering adenoviral sequences by the mouse H19 insulator, yields high and prostate-specific transgene expression both in cell cultures and when prostate cancer, PC-346C, tumors were grown orthotopically in nude mice. Intravenous virus administration reveals both higher activity and higher selectivity for the insulator-shielded PPT sequence than for the immediate-early CMV promoter. Therefore, we believe that an adenovirus with therapeutic gene expression controlled by an insulator-shielded PPT sequence is a promising candidate for gene therapy of prostate cancer.
Keyword
- Adenoviridae/*genetics
- Animals
- Cell Line; Tumor
- Enhancer Elements (Genetics)/genetics
- Gene Expression Regulation; Neoplastic
- Gene Therapy/*methods
- Genes; Reporter/genetics
- Genetic Vectors/genetics
- Humans
- Insulator Elements/genetics
- Luciferases/analysis/genetics
- Male
- Mice
- Neoplasms; Hormone-Dependent/genetics/*metabolism/therapy
- Nuclear Proteins/*genetics
- Promoter Regions (Genetics)/*genetics
- Prostatic Neoplasms/genetics/*metabolism/therapy
- Research Support; Non-U.S. Gov't
- Testosterone/metabolism
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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