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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Aberrant promoter methylation and expression of UTF1 during cervical carcinogenesis
PLoS ONE, Volume 7, No. 8, Article e42704, Year 2012
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Description
Promoter methylation profiles are proposed as potential prognosis and/or diagnosis biomarkers in cervical cancer. Up to now, little is known about the promoter methylation profile and expression pattern of stem cell (SC) markers during tumor development. In this study, we were interested to identify SC genes methylation profiles during cervical carcinogenesis. A genome-wide promoter methylation screening revealed a strong hypermethylation of Undifferentiated cell Transcription Factor 1 (UTF1) promoter in cervical cancer in comparison with normal ectocervix. By direct bisulfite pyrosequencing of DNA isolated from liquid-based cytological samples, we showed that UTF1 promoter methylation increases with lesion severity, the highest level of methylation being found in carcinoma. This hypermethylation was associated with increased UTF1 mRNA and protein expression. By using quantitative RT-PCR and Western Blot, we showed that both UTF1 mRNA and protein are present in epithelial cancer cell lines, even in the absence of its two main described regulators Oct4A and Sox2. Moreover, by immunofluorescence, we confirmed the nuclear localisation of UTF1 in cell lines. Surprisingly, direct bisulfite pyrosequencing revealed that the inhibition of DNA methyltransferase by 5-aza-2′-deoxycytidine was associated with decreased UTF1 gene methylation and expression in two cervical cancer cell lines of the four tested. These findings strongly suggest that UTF1 promoter methylation profile might be a useful biomarker for cervical cancer diagnosis and raise the questions of its role during epithelial carcinogenesis and of the mechanisms regulating its expression. © 2012 Guenin et al.
Authors & Co-Authors
Guenin, Samuel
Belgium, Liege
Université de Liège
Mouallif, Mustapha
Belgium, Liege
Université de Liège
Morocco, Casablanca
Hassan Ii University of Casablanca
Deplus, Rachel
Belgium, Brussels
Free Universities of Brussels
Lampe, Xavier
Belgium, Brussels
Free Universities of Brussels
Krusy, Nathalie
Belgium, Liege
Université de Liège
Calonne, Emilie
Belgium, Brussels
Free Universities of Brussels
Delbecque, Katty
France, Bagnolet
Saft
Kridelka, Frédéric J.
France, Bagnolet
Saft
Fuks, François
Belgium, Brussels
Free Universities of Brussels
Ennaji, M. M.
Morocco, Casablanca
Hassan Ii University of Casablanca
Delvenne, Philippe O.
Belgium, Liege
Université de Liège
Statistics
Citations: 27
Authors: 11
Affiliations: 4
Identifiers
Doi:
10.1371/journal.pone.0042704
e-ISSN:
19326203
Research Areas
Cancer
Genetics And Genomics
Study Approach
Quantitative