ArticleCancer gene therapy2006
Targeting and killing of prostate cancer cells using lentiviral constructs containing a sequence recognized by translation factor eIF4E and a prostate-specific promoter.
Article in Cancer gene therapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 28 citations in OpenAlex.
- N7-methylguanosine modification: from regulatory roles to therapeutic implications in cancer.American journal of cancer research · 2023Review
- Strategies to Improve the Safety of iPSC-Derived β Cells for β Cell Replacement in Diabetes.Transplant international : official journal of the European Society for Organ Transplantation · 2022Review
- Promoter-Operating Targeted Expression of Gene Therapy in Cancer: Current Stage and Prospect.Molecular therapy. Nucleic acids · 2018Review
- Targeting of protein translation as a new treatment paradigm for prostate cancer.Current opinion in oncology · 2017Article
- Article
- Fibroblast growth factor and ornithine decarboxylase 5'UTRs enable preferential expression in human prostate cancer cells and in prostate tumors of PTEN(-/-) transgenic mice.Cancer gene therapy · 2012Article
- AKT/mTOR as Novel Targets of Polyphenol Piceatannol Possibly Contributing to Inhibition of Proliferation of Cultured Prostate Cancer Cells.ISRN urology · 2012Article
- Transcriptional and translational dual-regulated oncolytic herpes simplex virus type 1 for targeting prostate tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- Carboxypeptidase-G2-based gene-directed enzyme-prodrug therapy: a new weapon in the GDEPT armoury.Nature reviews. Cancer · 2007Review
- Mechanisms of translational deregulation in human tumors and therapeutic intervention strategies.Oncogene · 2007Review
- An HSV-1 amplicon system for prostate-specific expression of ICP4 to complement oncolytic viral replication for in vitro and in vivo treatment of prostate cancer cells.Cancer gene therapy · 2007Article
- Review
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To develop a gene therapy that would selectively kill prostate cancer cells while sparing normal cells, we have constructed lentiviral vectors that contain a therapeutic gene with a short DNA sequence in the 5'-untranslated region (UTR) that is recognized by the translation initiation factor, eIF4E, which is often overexpressed in malignant cells. Infection of cancer (LNCaP, PC-3M, DU145, and MCF-7 cells) and noncancer cell lines (BPH-1, 267-B1, Plat-E, and Huvec-c cells) with lentivirus having a CMV-promoter and EGFP reporter resulted in high levels of EGFP expression in all cells, whereas, inclusion of the eIF4E UTR recognition sequence restricted high expression to cancer cells and Plat-E cells, which also express substantial levels of eIF4E. Infection of the cells with lentiviral vectors having this UTR in front of the HSV thymidine kinase suicide gene resulted in differential sensitivity to the killing effects of ganciclovir, with at least 100-fold more drug required to kill noncancer cells than cancer cells. Furthermore, in experiments where the CMV promoter was replaced by the prostate-specific ARR(2)PB promoter, the killing effects of ganciclovir were restricted to prostate cancer cells and not seen in nonprostate cancer cells. Our results indicate that combined translational regulation, by incorporation of an eIF4E-UTR recognition sequence into a therapeutic gene, together with transcriptional regulation with a prostate-specific promoter, may provide a means to selectively destroy prostate cancer cells while sparing normal prostate cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.