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Hypermethylation of the hTERT promoter inhibits the expression of telomerase activity in normal oral fibroblasts and senescent normal oral keratinocytes
- Source :
- British Journal of Cancer
- Publication Year :
- 2003
- Publisher :
- Springer Science and Business Media LLC, 2003.
-
Abstract
- Telomerase activity in human cells closely correlates with the expression of its catalytic subunit, telomerase reverse transcriptase (hTERT). Previously, we reported the lack of telomerase activity in normal human oral fibroblasts (NHOF) and the diminution of telomerase activity during senescence in normal human oral keratinocytes (NHOK). To investigate the underlying mechanisms of telomerase regulation in both cell types, we analysed the expression, promoter activity, and methylation status of the hTERT gene. The expression of hTERT mRNA diminished in senescent NHOK, but was not detected in NHOF at any stage of replication. An exogenous hTERT promoter was active in NHOF and in senescing NHOK, indicating that the lack of hTERT gene expression resulted from alteration of the endogenous hTERT promoter. Since methylation is involved in the silencing of numerous genes, we carried out DNA methylation assays. The assay revealed that the hTERT promoter was hypermethylated in NHOF and was gradually methylated during senescence in NHOK. Treatment of NHOF and senescent NHOK with the demethylating agent 5-aza-2'-deoxycytidine restored the expression of endogenous hTERT mRNA. Our results suggest that hypermethylation of the hTERT promoter plays a critical role in the negative regulation of telomerase activity in normal human oral cells.
- Subjects :
- Keratinocytes
Cancer Research
Telomerase
senescence
cells
Cell Culture Techniques
Biology
chemistry.chemical_compound
Catalytic Domain
Humans
Gene silencing
Telomerase reverse transcriptase
Promoter Regions, Genetic
neoplasms
Regulation of gene expression
Mouth
Molecular and Cellular Pathology
Methylation
DNA Methylation
Fibroblasts
Molecular biology
Demethylating agent
hypermethylation
DNA-Binding Proteins
enzymes and coenzymes (carbohydrates)
Gene Expression Regulation
Oncology
chemistry
Cell culture
embryonic structures
DNA methylation
Cancer research
biological phenomena, cell phenomena, and immunity
hTERT
Subjects
Details
- ISSN :
- 15321827 and 00070920
- Volume :
- 89
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....539161d1fd5cd2b9808f19c2d22a69bd