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Tumor Restrictive Suicide Gene Therapy for Glioma Controlled by the FOS Promoter
Effective suicide gene delivery and expression are crucial to achieving successful effects in gene therapy. An ideal tumor-specific promoter expresses therapeutic genes in tumor cells with minimal normal tissue expression. We compared the activity of the FOS (FBJ murine osteosarcoma viral oncogene h...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4646428/ https://www.ncbi.nlm.nih.gov/pubmed/26571389 http://dx.doi.org/10.1371/journal.pone.0143112 |
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author | Pan, Jianqing Wang, Hao Liu, Xinmin Hu, Jiliang Song, Weijian Luo, Jie Jiang, Shan Yan, Fei Zhai, Baojin |
author_facet | Pan, Jianqing Wang, Hao Liu, Xinmin Hu, Jiliang Song, Weijian Luo, Jie Jiang, Shan Yan, Fei Zhai, Baojin |
author_sort | Pan, Jianqing |
collection | PubMed |
description | Effective suicide gene delivery and expression are crucial to achieving successful effects in gene therapy. An ideal tumor-specific promoter expresses therapeutic genes in tumor cells with minimal normal tissue expression. We compared the activity of the FOS (FBJ murine osteosarcoma viral oncogene homolog) promoter with five alternative tumor-specific promoters in glioma cells and non-malignant astrocytes. The FOS promoter caused significantly higher transcriptional activity in glioma cell lines than all alternative promoters with the exception of CMV. The FOS promoter showed 13.9%, 32.4%, and 70.8% of the transcriptional activity of CMV in three glioma cell lines (U87, U251, and U373). Importantly, however, the FOS promoter showed only 1.6% of the transcriptional activity of CMV in normal astrocytes. We also tested the biologic activity of recombinant adenovirus containing the suicide gene herpes simplex virus thymidine kinase (HSV-tk) driven by the FOS promoter, including selective killing efficacy in vitro and tumor inhibition rate in vivo. Adenoviral-mediated delivery of the HSV-tk gene controlled by the FOS promoter conferred a cytotoxic effect on human glioma cells in vitro and in vivo. This study suggests that use of the FOS-tk adenovirus system is a promising strategy for glioma-specific gene therapy but still much left for improvement. |
format | Online Article Text |
id | pubmed-4646428 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-46464282015-11-25 Tumor Restrictive Suicide Gene Therapy for Glioma Controlled by the FOS Promoter Pan, Jianqing Wang, Hao Liu, Xinmin Hu, Jiliang Song, Weijian Luo, Jie Jiang, Shan Yan, Fei Zhai, Baojin PLoS One Research Article Effective suicide gene delivery and expression are crucial to achieving successful effects in gene therapy. An ideal tumor-specific promoter expresses therapeutic genes in tumor cells with minimal normal tissue expression. We compared the activity of the FOS (FBJ murine osteosarcoma viral oncogene homolog) promoter with five alternative tumor-specific promoters in glioma cells and non-malignant astrocytes. The FOS promoter caused significantly higher transcriptional activity in glioma cell lines than all alternative promoters with the exception of CMV. The FOS promoter showed 13.9%, 32.4%, and 70.8% of the transcriptional activity of CMV in three glioma cell lines (U87, U251, and U373). Importantly, however, the FOS promoter showed only 1.6% of the transcriptional activity of CMV in normal astrocytes. We also tested the biologic activity of recombinant adenovirus containing the suicide gene herpes simplex virus thymidine kinase (HSV-tk) driven by the FOS promoter, including selective killing efficacy in vitro and tumor inhibition rate in vivo. Adenoviral-mediated delivery of the HSV-tk gene controlled by the FOS promoter conferred a cytotoxic effect on human glioma cells in vitro and in vivo. This study suggests that use of the FOS-tk adenovirus system is a promising strategy for glioma-specific gene therapy but still much left for improvement. Public Library of Science 2015-11-16 /pmc/articles/PMC4646428/ /pubmed/26571389 http://dx.doi.org/10.1371/journal.pone.0143112 Text en © 2015 Pan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Pan, Jianqing Wang, Hao Liu, Xinmin Hu, Jiliang Song, Weijian Luo, Jie Jiang, Shan Yan, Fei Zhai, Baojin Tumor Restrictive Suicide Gene Therapy for Glioma Controlled by the FOS Promoter |
title | Tumor Restrictive Suicide Gene Therapy for Glioma Controlled by the FOS Promoter |
title_full | Tumor Restrictive Suicide Gene Therapy for Glioma Controlled by the FOS Promoter |
title_fullStr | Tumor Restrictive Suicide Gene Therapy for Glioma Controlled by the FOS Promoter |
title_full_unstemmed | Tumor Restrictive Suicide Gene Therapy for Glioma Controlled by the FOS Promoter |
title_short | Tumor Restrictive Suicide Gene Therapy for Glioma Controlled by the FOS Promoter |
title_sort | tumor restrictive suicide gene therapy for glioma controlled by the fos promoter |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4646428/ https://www.ncbi.nlm.nih.gov/pubmed/26571389 http://dx.doi.org/10.1371/journal.pone.0143112 |
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