Targeted therapy of DNA tumor virus-associated cancers using virus-activated transcription factors

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dc.contributor.authorM J Lim-
dc.contributor.authorS H Min-
dc.contributor.authorJ J Lee-
dc.contributor.authorI C Kim-
dc.contributor.authorJ T Kim-
dc.contributor.authorDong Chul Lee-
dc.contributor.authorNam-Soon Kim-
dc.contributor.authorS Jeong-
dc.contributor.authorM N Kim-
dc.contributor.authorK D Kim-
dc.contributor.authorJ S Lim-
dc.contributor.authorSang Bae Han-
dc.contributor.authorHwan Mook Kim-
dc.contributor.authorD S Heo-
dc.contributor.authorYoung Il Yeom-
dc.date.accessioned2017-04-19T09:04:40Z-
dc.date.available2017-04-19T09:04:40Z-
dc.date.issued2006-
dc.identifier.issn1525-0016-
dc.identifier.uri10.1016/j.ymthe.2005.11.023ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/7445-
dc.description.abstractDNA tumor virus-mediated tumorigenic processes typically involve functional inactivation of cellular tumor suppressors pRB and p53 by viral oncoproteins, with concomitant activation of oncogenic transcription factors such as E2Fs. This feature could be exploited to design a treatment for corresponding malignancies. Here, we report a gene therapy strategy for DNA tumor virus-associated cancers using a synthetic, E2F-regulated gene expression system named pESM6. This system contains multimerized E2F-responsive elements in combination with the binding sites for ubiquitous transcription factors Sp1 and CTF/NF1. pESM6 could drive a high-level transgene expression comparable to that of the CMV IE promoter and exert constitutive activity in cells expressing DNA tumor viral oncogenes. In contrast, it was effectively repressed by pRB and thus only minimally active in nontransformed cells. Expression of cytosine deaminase from pESM6 resulted in a highly efficient and specific killing of HPV-transformed fibroblasts (C3) after treatment with the prodrug 5-fluorocytosine. Also, an effective tumor mass reduction was observed when the vector was injected directly into C3 tumors implanted in C57BL/6 mice. pESM6 showed a superior performance throughout these experiments compared to the previously known E2F-regulated gene vector. These results clearly demonstrate the potential usability of pESM6 for the gene therapy of DNA tumor virus-associated cancers.-
dc.publisherElsevier-Cell Press-
dc.titleTargeted therapy of DNA tumor virus-associated cancers using virus-activated transcription factors-
dc.title.alternativeTargeted therapy of DNA tumor virus-associated cancers using virus-activated transcription factors-
dc.typeArticle-
dc.citation.titleMolecular Therapy-
dc.citation.number5-
dc.citation.endPage909-
dc.citation.startPage899-
dc.citation.volume13-
dc.contributor.affiliatedAuthorDong Chul Lee-
dc.contributor.affiliatedAuthorNam-Soon Kim-
dc.contributor.affiliatedAuthorSang Bae Han-
dc.contributor.affiliatedAuthorHwan Mook Kim-
dc.contributor.affiliatedAuthorYoung Il Yeom-
dc.contributor.alternativeName임미정-
dc.contributor.alternativeName민상현-
dc.contributor.alternativeName이재정-
dc.contributor.alternativeName김일철-
dc.contributor.alternativeName김지태-
dc.contributor.alternativeName이동철-
dc.contributor.alternativeName김남순-
dc.contributor.alternativeName정상균-
dc.contributor.alternativeName김미나-
dc.contributor.alternativeName김광동-
dc.contributor.alternativeName임종석-
dc.contributor.alternativeName한상배-
dc.contributor.alternativeName김환묵-
dc.contributor.alternativeName허대석-
dc.contributor.alternativeName염영일-
dc.identifier.bibliographicCitationMolecular Therapy, vol. 13, no. 5, pp. 899-909-
dc.identifier.doi10.1016/j.ymthe.2005.11.023-
dc.subject.keywordcancer-
dc.subject.keywordDNA tumor virus-
dc.subject.keywordE2F transcription factors-
dc.subject.keywordgene therapy-
dc.subject.keywordtumor-specific gene expression-
dc.subject.localCancers-
dc.subject.localcancer-
dc.subject.localCancer-
dc.subject.localDNA tumor virus-
dc.subject.localE2F transcription factor-
dc.subject.localE2F transcription factors-
dc.subject.localGene Therapy-
dc.subject.localgene therapy-
dc.subject.localGene therapy-
dc.subject.localtumor-specific gene expression-
dc.description.journalClassY-
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
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