ArticleBMC cancer2010
hTERT promoter activity and CpG methylation in HPV-induced carcinogenesis.
Article in BMC cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 62 citations in OpenAlex.
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- DNA methylation markers in esophageal cancer: an emerging tool for cancer surveillance and treatment.American journal of cancer research · 2021Review
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- A Study of hTERT Promoter Methylation in Circulating Tumour DNAs of Patients with Ovarian Magnificent Tumour.OncoTargets and therapy · 2020Article
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- Molecular mechanisms in progression of HPV-associated cervical carcinogenesis.Journal of biomedical science · 2019Review
- hTERT promoter methylation status in peripheral blood leukocytes as a molecular marker of head and neck cancer progression.Journal of applied genetics · 2018Article
- Telomeres and Telomerase During Human Papillomavirus-Induced Carcinogenesis.Molecular diagnosis & therapy · 2018Review
- DNA Tumor Virus Regulation of Host DNA Methylation and Its Implications for Immune Evasion and Oncogenesis.Viruses · 2018Review
- Telomerase activity in cervical scrapes of women with high-grade cervical disease: A nested case-control study.Oncology letters · 2018Article
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- Telomerase Induction in HPV Infection and Oncogenesis.Viruses · 2017Review
- High-Risk Human Papillomavirus E7 Alters Host DNA Methylome and Represses HLA-E Expression in Human Keratinocytes.Scientific reports · 2017Article
- Detection of Aberrant TERT Promoter Methylation by Combined Bisulfite Restriction Enzyme Analysis for Cancer Diagnosis.The Journal of molecular diagnostics : JMD · 2017Article
- DNA Oncogenic Virus-Induced Oxidative Stress, Genomic Damage, and Aberrant Epigenetic Alterations.Oxidative medicine and cellular longevity · 2017Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundActivation of telomerase resulting from deregulated hTERT expression is a key event during high-risk human papillomavirus (hrHPV)-induced cervical carcinogenesis. In the present study we examined hTERT promoter activity and its relation to DNA methylation as one of the potential mechanisms underlying deregulated hTERT transcription in hrHPV-transformed cells.
methodsUsing luciferase reporter assays we analyzed hTERT promoter activity in primary keratinocytes, HPV16- and HPV18-immortalized keratinocyte cell lines and cervical cancer cell lines. In the same cells as well as cervical specimens we determined hTERT methylation by bisulfite sequencing analysis of the region spanning -442 to +566 (relative to the ATG) and quantitative methylation specific PCR (qMSP) analysis of two regions flanking the hTERT core promoter.
resultsWe found that in most telomerase positive cells increased hTERT core promoter activity coincided with increased hTERT mRNA expression. On the other hand basal hTERT promoter activity was also detected in telomerase negative cells with no or strongly reduced hTERT mRNA expression levels. In both telomerase positive and negative cells regulatory sequences flanking both ends of the core promoter markedly repressed exogenous promoter activity.By extensive bisulfite sequencing a strong increase in CpG methylation was detected in hTERT positive cells compared to cells with no or strongly reduced hTERT expression. Subsequent qMSP analysis of a larger set of cervical tissue specimens revealed methylation of both regions analyzed in 100% of cervical carcinomas and 38% of the high-grade precursor lesions, compared to 9% of low grade precursor lesions and 5% of normal controls.
conclusionsMethylation of transcriptionally repressive sequences in the hTERT promoter and proximal exonic sequences is correlated to deregulated hTERT transcription in HPV-immortalized cells and cervical cancer cells. The detection of DNA methylation at these repressive regions may provide an attractive biomarker for early detection of cervical cancer.
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