Aberrant promoter methylation and expression of UTF1 during cervical carcinogenesis.
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3411846?pdf=render |
| _version_ | 1811222535719616512 |
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| author | Samuel Guenin Mustapha Mouallif Rachel Deplus Xavier Lampe Nathalie Krusy Emilie Calonne Katty Delbecque Frederic Kridelka François Fuks My Mustapha Ennaji Philippe Delvenne |
| author_facet | Samuel Guenin Mustapha Mouallif Rachel Deplus Xavier Lampe Nathalie Krusy Emilie Calonne Katty Delbecque Frederic Kridelka François Fuks My Mustapha Ennaji Philippe Delvenne |
| author_sort | Samuel Guenin |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T08:17:30Z |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T08:17:30Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4d38725939264037b81b3a189d99caf52022-12-22T03:40:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4270410.1371/journal.pone.0042704Aberrant promoter methylation and expression of UTF1 during cervical carcinogenesis.Samuel GueninMustapha MouallifRachel DeplusXavier LampeNathalie KrusyEmilie CalonneKatty DelbecqueFrederic KridelkaFrançois FuksMy Mustapha EnnajiPhilippe DelvennePromoter 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.http://europepmc.org/articles/PMC3411846?pdf=render |
| spellingShingle | Samuel Guenin Mustapha Mouallif Rachel Deplus Xavier Lampe Nathalie Krusy Emilie Calonne Katty Delbecque Frederic Kridelka François Fuks My Mustapha Ennaji Philippe Delvenne Aberrant promoter methylation and expression of UTF1 during cervical carcinogenesis. PLoS ONE |
| title | Aberrant promoter methylation and expression of UTF1 during cervical carcinogenesis. |
| title_full | Aberrant promoter methylation and expression of UTF1 during cervical carcinogenesis. |
| title_fullStr | Aberrant promoter methylation and expression of UTF1 during cervical carcinogenesis. |
| title_full_unstemmed | Aberrant promoter methylation and expression of UTF1 during cervical carcinogenesis. |
| title_short | Aberrant promoter methylation and expression of UTF1 during cervical carcinogenesis. |
| title_sort | aberrant promoter methylation and expression of utf1 during cervical carcinogenesis |
| url | http://europepmc.org/articles/PMC3411846?pdf=render |
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