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Article: Promoter hypermethylation and histone hypoacetylation contribute to pancreatic-duodenal homeobox 1 silencing in gastric cancer

TitlePromoter hypermethylation and histone hypoacetylation contribute to pancreatic-duodenal homeobox 1 silencing in gastric cancer
Authors
Issue Date2010
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
Citation
Carcinogenesis, 2010, v. 31 n. 9, p. 1552-1560 How to Cite?
Abstract
Background 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.
Persistent Identifierhttp://hdl.handle.net/10722/124948
ISSN
2013 Impact Factor: 5.266
ISI Accession Number ID
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).

References

 

Author Affiliations
  1. Guangzhou General Hospital of Guangzhou Command
  2. The University of Hong Kong
  3. Sun Yat-Sen University
DC FieldValueLanguage
dc.contributor.authorMa, Jen_HK
dc.contributor.authorWang, JDen_HK
dc.contributor.authorZhang, WJen_HK
dc.contributor.authorZou, Ben_HK
dc.contributor.authorChen, WJen_HK
dc.contributor.authorLam, CSCen_HK
dc.contributor.authorChen, MHen_HK
dc.contributor.authorPang, Ren_HK
dc.contributor.authorTan, VPYen_HK
dc.contributor.authorHung, IFen_HK
dc.contributor.authorLan, HYen_HK
dc.contributor.authorWang, QYen_HK
dc.contributor.authorWong, BCYen_HK
dc.date.accessioned2010-10-31T11:03:04Z-
dc.date.available2010-10-31T11:03:04Z-
dc.date.issued2010en_HK
dc.identifier.citationCarcinogenesis, 2010, v. 31 n. 9, p. 1552-1560en_HK
dc.identifier.issn0143-3334en_HK
dc.identifier.urihttp://hdl.handle.net/10722/124948-
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.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/en_HK
dc.relation.ispartofCarcinogenesisen_HK
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 canceren_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0143-3334&volume=31&issue=9&spage=1552&epage=1560&date=2010&atitle=Promoter+hypermethylation+and+histone+hypoacetylation+contribute+to+Pancreatic-duodenal+homeobox+1+(PDX1)+silencing+in+gastric+canceren_HK
dc.identifier.emailWang, JD: jidewang@gmail.comen_HK
dc.identifier.emailPang, R: robertap@hku.hken_HK
dc.identifier.emailTan, VPY: vpytan@hku.hken_HK
dc.identifier.emailHung, IF: ivanhung@hkucc.hku.hken_HK
dc.identifier.emailWong, BCY: bcywong@hku.hken_HK
dc.identifier.authorityWang, JD=rp00491en_HK
dc.identifier.authorityPang, R=rp00274en_HK
dc.identifier.authorityTan, VPY=rp01458en_HK
dc.identifier.authorityHung, IF=rp00508en_HK
dc.identifier.authorityWong, BCY=rp00429en_HK
dc.description.naturepostprint-
dc.identifier.doi10.1093/carcin/bgq140en_HK
dc.identifier.pmid20622005en_HK
dc.identifier.scopuseid_2-s2.0-77956290718en_HK
dc.identifier.hkuros174515en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77956290718&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume31en_HK
dc.identifier.issue9en_HK
dc.identifier.spage1552en_HK
dc.identifier.epage1560en_HK
dc.identifier.isiWOS:000281530400007-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridMa, J=35275386200en_HK
dc.identifier.scopusauthoridWang, JD=35309087500en_HK
dc.identifier.scopusauthoridZhang, WJ=39462500000en_HK
dc.identifier.scopusauthoridZou, B=35228257300en_HK
dc.identifier.scopusauthoridChen, WJ=39461087400en_HK
dc.identifier.scopusauthoridLam, CSC=35332626500en_HK
dc.identifier.scopusauthoridChen, MH=8642044500en_HK
dc.identifier.scopusauthoridPang, R=7004376659en_HK
dc.identifier.scopusauthoridTan, VPY=24449627600en_HK
dc.identifier.scopusauthoridHung, IF=7006103457en_HK
dc.identifier.scopusauthoridLan, HY=24544799000en_HK
dc.identifier.scopusauthoridWang, QY=36505083100en_HK
dc.identifier.scopusauthoridWong, BCY=7402023340en_HK
dc.identifier.citeulike7842378-

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