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Preferentially enhanced gene expression from a synthetic human telomerase reverse transcriptase promoter in human cancer cells
- Source :
- Oncology Reports.
- Publication Year :
- 2006
- Publisher :
- Spandidos Publications, 2006.
-
Abstract
- Although the human telomerase reverse transcriptase (hTERT) promoter can regulate cancer-specific genes, it is generally too weak to be effective. We therefore attempted to improve the potency of synthetic hTERT promoters by fusing the core element (E) of the hTERT promoter (H) and the tripartite leader sequence (T) from human adenovirus 5 in a combinatorial manner. To determine the potential as cancer-specific promoters, we measured luciferase activity driven by the chimeric hTERT promoters in human cancer cells. Among various constructs, the E3-H-T promoter induced the strongest luciferase activity in all the tested cancer cells. SK-Hep1 and Hela cells experienced 1000- and 11-fold higher expression than the basic hTERT promoter, respectively. Relative to the SV40 universal promoter, the E3-H-T promoter led to higher levels of gene expression. Using EMSA, we found that the hTERT enhancer region was specifically bound to c-Myc and Sp1. Thus, the data suggest that the E3-H-T promoter with up-regulated cancer-specific gene expression could be useful in cancer gene therapy.
- Subjects :
- Cancer Research
Telomerase
Sp1 Transcription Factor
Adenoviruses, Human
Promoter
Genetic Therapy
General Medicine
Biology
Molecular biology
DNA-Binding Proteins
Gene Expression Regulation, Neoplastic
Oncology
Regulatory sequence
Cell Line, Tumor
Neoplasms
Gene expression
Humans
Telomerase reverse transcriptase
Luciferase
Promoter Regions, Genetic
Enhancer
Gene
HeLa Cells
Transcription Factors
Subjects
Details
- ISSN :
- 17912431 and 1021335X
- Database :
- OpenAIRE
- Journal :
- Oncology Reports
- Accession number :
- edsair.doi.dedup.....593a7783c874f9c99f16cb46bc2a4c54