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A novel TARP-promot...
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Cheng, Wing-ShingUppsala universitet,Enheten för klinisk immunologi
(författare)
A novel TARP-promoter-based adenovirus against hormone-dependent and hormone-refractory prostate cancer
- Artikel/kapitelEngelska2004
Förlag, utgivningsår, omfång ...
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Elsevier BV,2004
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-92861
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-92861URI
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https://doi.org/10.1016/j.ymthe.2004.05.022DOI
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Språk:engelska
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Sammanfattning på:engelska
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Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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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.
Ämnesord och genrebeteckningar
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Adenoviridae/*genetics
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Animals
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Cell Line; Tumor
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Enhancer Elements (Genetics)/genetics
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Gene Expression Regulation; Neoplastic
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Gene Therapy/*methods
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Genes; Reporter/genetics
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Genetic Vectors/genetics
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Humans
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Insulator Elements/genetics
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Luciferases/analysis/genetics
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Male
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Mice
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Neoplasms; Hormone-Dependent/genetics/*metabolism/therapy
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Nuclear Proteins/*genetics
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Promoter Regions (Genetics)/*genetics
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Prostatic Neoplasms/genetics/*metabolism/therapy
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Research Support; Non-U.S. Gov't
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Testosterone/metabolism
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MEDICINE
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MEDICIN
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Kraaij, Robert
(författare)
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Nilsson, BerithUppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi(Swepub:uu)benil498
(författare)
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van der Weel, Laura
(författare)
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de Ridder, Corrina M.A.
(författare)
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Tötterman, Thomas H.Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi(Swepub:uu)thomtott
(författare)
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Essand, MagnusUppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi(Swepub:uu)magnessa
(författare)
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Uppsala universitetEnheten för klinisk immunologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Molecular Therapy: Elsevier BV10:2, s. 355-3641525-00161525-0024
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