| An oncolytic adenovirus controlled by a modified telomerase promoter is attenuated in telomerase-negative cells, but shows reduced activity in cancer cells. | |
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MedLine Citation:
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PMID: 15976917 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The promoter for human telomerase reverse transcriptase (hTERTp) is preferentially active in malignant cells. It was recently used to control the expression of the adenoviral E1A gene for the development of oncolytic adenoviruses. To ensure maximal repression in normal cells, the inclusion of additional E-boxes in the proximal region of the core promoter was described. We found that the transcriptional activity of this artificial sequence (T-255-4DEB) is minimal in normal cells, but it is also reduced in all the cancer cell lines tested. The cancer specificity of a new oncolytic adenovirus based in this promoter (AdTE1) was evaluated by direct comparison with wild-type adenovirus type 5 (AdWT) in vitro and in vivo. In all the parameters tested, AdTE1 was attenuated in normal cells, but the efficacy in cancer cells showed a parallel reduction, suggesting a lack of specificity. However, the cytotoxicity of AdTE1 was repressed in senescent cells compared to AdWT. Therefore, we conclude that AdTE1 is preferentially attenuated only in cells that are permanently devoid of telomerase expression such as senescent cells. Further modifications in the telomerase-based promoters should be introduced in order to combine maximal attenuation of oncolytic adenoviruses in normal tissues and enhanced activity in tumors. |
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Authors:
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S Bortolanza; C Qian; M G Kramer; C Gomar; J Prieto; F Farinati; R Hernandez-Alcoceba |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-06-23 |
Journal Detail:
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Title: Journal of molecular medicine (Berlin, Germany) Volume: 83 ISSN: 0946-2716 ISO Abbreviation: J. Mol. Med. Publication Date: 2005 Sep |
Date Detail:
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Created Date: 2005-08-31 Completed Date: 2005-12-30 Revised Date: 2011-07-08 |
Medline Journal Info:
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Nlm Unique ID: 9504370 Medline TA: J Mol Med (Berl) Country: Germany |
Other Details:
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Languages: eng Pagination: 736-47 Citation Subset: IM |
Affiliation:
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Padua University Surgical and Gastroenterological Sciences, Padua, 35128, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae* Adenovirus E1A Proteins / biosynthesis, genetics* Cell Line, Tumor Gene Expression Regulation, Viral / genetics* Gene Therapy / methods Humans Neoplasms / enzymology*, genetics, therapy Promoter Regions, Genetic* Telomerase / genetics* |
| Chemical | |
Reg. No./Substance:
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0/Adenovirus E1A Proteins; EC 2.7.7.49/Telomerase |
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