ArticleCancer gene therapy2007
Two-step amplification of the human PPT sequence provides specific gene expression in an immunocompetent murine prostate cancer model.
Article in Cancer gene therapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 20 citations in OpenAlex.
- Targeting strategies of adenovirus‑mediated gene therapy and virotherapy for prostate cancer (Review).Molecular medicine reports · 2017Review
- A molecular imaging system based on both transcriptional and genomic amplification to detect prostate cancer cells in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Androgen-independent molecular imaging vectors to detect castration-resistant and metastatic prostate cancer.Cancer research · 2011Article
- In vivo imaging of intraprostatic-specific gene transcription by PET.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2011Article
- Noninvasive imaging of therapeutic gene expression using a bidirectional transcriptional amplification strategy.Molecular therapy : the journal of the American Society of Gene Therapy · 2008Article
- Configurations of a two-tiered amplified gene expression system in adenoviral vectors designed to improve the specificity of in vivo prostate cancer imaging.Gene therapy · 2008Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The recombinant prostate-specific PPT sequence comprises a prostate-specific antigen enhancer, a PSMA enhancer and a TARP promoter. It is transcriptionally active in human prostate cancer cells both in the presence and absence of testosterone. However, in experimental murine prostate cancer, it has no detectable transcriptional activity. Herein, we describe that the PPT sequence in combination with a two-step transcriptional amplification (TSTA) system becomes active also in murine prostate cancer cells. An adenovirus with TSTA-amplified PPT-controlled expression of the luciferase reporter gene, Ad[PPT/TSTA-Luc], has up to 100-fold higher prostate-specific transcriptional activity than a non-amplified PPT-based adenovirus, Ad[PPT-Luc], in human cells. In addition, Ad[PPT/TSTA-Luc] confers prostate-specific transgene expression in murine cells, with an activity that is approximately 23% of Ad[CMV-Luc] in the transgenic adenocarcinoma of the mouse prostate (TRAMP)-C2 cells. Moreover, to visualize luciferase expression in living mice a charge-coupled device camera was used. Ad[PPT/TSTA-Luc] yielded approximately 30-fold higher transgene expression than Ad[PPT-Luc] in LNCaP tumor xenografts. Importantly, Ad[PPT/TSTA-Luc] also showed activity in murine TRAMP-C2 tumors, whereas Ad[PPT-Luc] activity was undetectable. These results highlight that the recombinant PPT sequence is active in murine prostate cancer cells when augmented by a TSTA system. This finding opens up for preclinical studies with prostate-specific therapeutic gene expression in immunocompetent mice.
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