Article (Scientific journals)
Aberrant promoter methylation and expression of UTF1 during cervical carcinogenesis.
Guenin, Samuel; Mouallif, Mustapha; Deplus, Rachel et al.
2012In PLoS ONE, 7 (8), p. 42704
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Abstract :
[en] 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.
Disciplines :
Oncology
Author, co-author :
Guenin, Samuel
Mouallif, Mustapha ;  Université de Liège - ULiège > GIGA - Membres
Deplus, Rachel
Lampe, Xavier
Krusy, Nathalie
Calonne, Emilie
DELBECQUE, Katty ;  Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
Kridelka, Frédéric ;  Université de Liège - ULiège > Département des sciences cliniques > Gynécologie et obstétrique
Fuks, Francois
Ennaji, My Mustapha
Delvenne, Philippe ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Language :
English
Title :
Aberrant promoter methylation and expression of UTF1 during cervical carcinogenesis.
Publication date :
2012
Journal title :
PLoS ONE
eISSN :
1932-6203
Publisher :
Public Library of Science, United States - California
Volume :
7
Issue :
8
Pages :
e42704
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 22 October 2012

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