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Article: Promoter hypermethylation and histone hypoacetylation contribute to pancreatic-duodenal homeobox 1 silencing in gastric cancer
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TitlePromoter hypermethylation and histone hypoacetylation contribute to pancreatic-duodenal homeobox 1 silencing in gastric cancer
 
AuthorsMa, J3 1 2
Wang, JD2
Zhang, WJ2
Zou, B2
Chen, WJ2
Lam, CSC2
Chen, MH3
Pang, R2
Tan, VPY2
Hung, IF2
Lan, HY2
Wang, QY1
Wong, BCY2
 
Issue Date2010
 
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
 
CitationCarcinogenesis, 2010, v. 31 n. 9, p. 1552-1560 [How to Cite?]
DOI: http://dx.doi.org/10.1093/carcin/bgq140
 
AbstractBackground and Aims: The expression of pancreatic-duodenal homeobox 1 (PDX1) in gastric cancer is aberrantly reduced. The aim of this study was to elucidate the regulation of DNA methylation and histone acetylation at the promoter for PDX1 silencing in gastric cancer. Methods: PDX1 expression in response to demethylation and acetylation was detected in human gastric cancer cell lines by reverse transcription-polymerase chain reaction (PCR) and western blot. Four CpG islands within the 5#-flanking region of PDX1 gene were analyzed with their transcription activities being detected by dual luciferase assay. Promoter hypermethylation was identified in gastric cancer cell lines and cancer tissues by methylation-specific PCR or bisulfite DNA sequencing PCR analysis. Histone acetylation was determined by chromatin immunoprecipitation (ChIP) assay. Results: Demethylation by 5′-aza-2′-deoxycytidine (5′-aza-dC) and/or acetylation by trichostatin A (TSA) restored PDX1 expression in gastric cancer cells. Hypermethylation was found in four CpG islands in six of seven cancer cell lines. However, only the distal CpG island located in the promoter fragment of PDX1, F383 (c.22063 to 21681 nt upstream of the ATG start codon) displayed significant transcriptional activity that could be suppressed by SssI methylase and increased by 5′-aza-dC and TSA. More than 70% of the single CpG sites in F383 were methylated with hypermethylation of F383 fragment more common in gastric cancerous tissues compared with the paired normal tissues (P < 0.05). ChIP assay showed F383 was also associated with low hypoacetylation level of the histones. Conclusion: Promoter hypermethylation and histone hypoacetylation contribute to PDX1 silencing in gastric cancer. © The Author 2010. Published by Oxford University Press. All rights reserved.
 
ISSN0143-3334
2013 Impact Factor: 5.266
 
DOIhttp://dx.doi.org/10.1093/carcin/bgq140
 
ISI Accession Number IDWOS:000281530400007
Funding AgencyGrant Number
Simon K.Y.Lee endowed professorship Research Fund
Gordon Chiu Stomach Cancer Research Fund
University of Hong Kong, Hong Kong
National Basic Research Program of China (973 Program)2010CB529306
Doctoral Program Fund
Guangdong natural science fund
Guangdong General Hospital9451008004002824
Funding Information:

Simon K.Y.Lee endowed professorship Research Fund; Gordon Chiu Stomach Cancer Research Fund; Outstanding Researcher Award Fund of the University of Hong Kong, Hong Kong; National Basic Research Program of China (973 Program) (2010CB529306); Doctoral Program Fund; Guangdong natural science fund; Guangdong General Hospital (9451008004002824).

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorMa, J
 
dc.contributor.authorWang, JD
 
dc.contributor.authorZhang, WJ
 
dc.contributor.authorZou, B
 
dc.contributor.authorChen, WJ
 
dc.contributor.authorLam, CSC
 
dc.contributor.authorChen, MH
 
dc.contributor.authorPang, R
 
dc.contributor.authorTan, VPY
 
dc.contributor.authorHung, IF
 
dc.contributor.authorLan, HY
 
dc.contributor.authorWang, QY
 
dc.contributor.authorWong, BCY
 
dc.date.accessioned2010-10-31T11:03:04Z
 
dc.date.available2010-10-31T11:03:04Z
 
dc.date.issued2010
 
dc.description.abstractBackground and Aims: The expression of pancreatic-duodenal homeobox 1 (PDX1) in gastric cancer is aberrantly reduced. The aim of this study was to elucidate the regulation of DNA methylation and histone acetylation at the promoter for PDX1 silencing in gastric cancer. Methods: PDX1 expression in response to demethylation and acetylation was detected in human gastric cancer cell lines by reverse transcription-polymerase chain reaction (PCR) and western blot. Four CpG islands within the 5#-flanking region of PDX1 gene were analyzed with their transcription activities being detected by dual luciferase assay. Promoter hypermethylation was identified in gastric cancer cell lines and cancer tissues by methylation-specific PCR or bisulfite DNA sequencing PCR analysis. Histone acetylation was determined by chromatin immunoprecipitation (ChIP) assay. Results: Demethylation by 5′-aza-2′-deoxycytidine (5′-aza-dC) and/or acetylation by trichostatin A (TSA) restored PDX1 expression in gastric cancer cells. Hypermethylation was found in four CpG islands in six of seven cancer cell lines. However, only the distal CpG island located in the promoter fragment of PDX1, F383 (c.22063 to 21681 nt upstream of the ATG start codon) displayed significant transcriptional activity that could be suppressed by SssI methylase and increased by 5′-aza-dC and TSA. More than 70% of the single CpG sites in F383 were methylated with hypermethylation of F383 fragment more common in gastric cancerous tissues compared with the paired normal tissues (P < 0.05). ChIP assay showed F383 was also associated with low hypoacetylation level of the histones. Conclusion: Promoter hypermethylation and histone hypoacetylation contribute to PDX1 silencing in gastric cancer. © The Author 2010. Published by Oxford University Press. All rights reserved.
 
dc.description.naturepostprint
 
dc.identifier.citationCarcinogenesis, 2010, v. 31 n. 9, p. 1552-1560 [How to Cite?]
DOI: http://dx.doi.org/10.1093/carcin/bgq140
 
dc.identifier.citeulike7842378
 
dc.identifier.doihttp://dx.doi.org/10.1093/carcin/bgq140
 
dc.identifier.epage1560
 
dc.identifier.hkuros174515
 
dc.identifier.isiWOS:000281530400007
Funding AgencyGrant Number
Simon K.Y.Lee endowed professorship Research Fund
Gordon Chiu Stomach Cancer Research Fund
University of Hong Kong, Hong Kong
National Basic Research Program of China (973 Program)2010CB529306
Doctoral Program Fund
Guangdong natural science fund
Guangdong General Hospital9451008004002824
Funding Information:

Simon K.Y.Lee endowed professorship Research Fund; Gordon Chiu Stomach Cancer Research Fund; Outstanding Researcher Award Fund of the University of Hong Kong, Hong Kong; National Basic Research Program of China (973 Program) (2010CB529306); Doctoral Program Fund; Guangdong natural science fund; Guangdong General Hospital (9451008004002824).

 
dc.identifier.issn0143-3334
2013 Impact Factor: 5.266
 
dc.identifier.issue9
 
dc.identifier.openurl
 
dc.identifier.pmid20622005
 
dc.identifier.scopuseid_2-s2.0-77956290718
 
dc.identifier.spage1552
 
dc.identifier.urihttp://hdl.handle.net/10722/124948
 
dc.identifier.volume31
 
dc.languageeng
 
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofCarcinogenesis
 
dc.relation.referencesReferences in Scopus
 
dc.rightsThis is a pre-copy-editing, author-produced PDF of an article accepted for publication in Carcinogenesis following peer review. The definitive publisher-authenticated version Carcinogenesis, 2010, v. 31 n. 9, p. 1552-1560 is available online at: http://carcin.oxfordjournals.org/content/31/9/1552
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subject.meshDNA Methylation
 
dc.subject.meshGene Silencing
 
dc.subject.meshHomeodomain Proteins - genetics - metabolism
 
dc.subject.meshStomach Neoplasms - genetics
 
dc.subject.meshTrans-Activators - genetics - metabolism
 
dc.titlePromoter hypermethylation and histone hypoacetylation contribute to pancreatic-duodenal homeobox 1 silencing in gastric cancer
 
dc.typeArticle
 
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<contributor.author>Chen, WJ</contributor.author>
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<subject.mesh>DNA Methylation</subject.mesh>
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Author Affiliations
  1. Guangzhou General Hospital of Guangzhou Command
  2. The University of Hong Kong
  3. Sun Yat-Sen University