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Article: Characterization of tumor suppressive function of P300/CBP-associated factor at frequently deleted region 3p24 in esophageal squamous cell carcinoma

TitleCharacterization of tumor suppressive function of P300/CBP-associated factor at frequently deleted region 3p24 in esophageal squamous cell carcinoma
Authors
KeywordsEsophageal squamous cell carcinoma
Loss of heterozygosity
Methylation
PCAF
Tumor suppressor gene
Issue Date2009
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2009, v. 28 n. 31, p. 2821-2828 How to Cite?
AbstractDeletion of 3p is one of the most frequent genetic alterations in many tumors, including esophageal squamous cell carcinoma (ESCC). In our recent study, deletion of 3p24 was frequently detected in ESCC and one candidate tumor suppressor gene (TSG), p300/CBP-associated factor (PCAF), was identified within the region. In this study, downregulation of PCAF was detected in 23/40 (57.5%) of primary ESCCs and 4/9 (44.4%) of the ESCC cell lines. A further study found that downregulation of PCAF was also associated with hypermethylation of the promoter region of PCAF gene. Methylation-specific PCR found that promoter methylation was detected in 28/40 (70%) of primary ESCCs and 5/9 (55.6%) of ESCC cell lines. In addition, the expression of PCAF could be reactivated in ESCC cell line KYSE510 after demethylation treatment with 5-aza-dC. Functional studies showed that PCAF was able to suppress tumorigenicity of ESCC cells both in vitro and in vivo, including foci formation, colony formation in soft agar and tumor formation in nude mice. Molecular study found that the tumor suppressive mechanism of PCAF was associated with its role in cell cycle arrest at the G1/S checkpoint by the downregulation of CDK2 and upregulation of p21 waf1/Cip1, Smad4, Rb and p27 Kip1. In conclusion, PCAF might be the target TSG responsible for the 3p24 deletion event, which has an important role in the development and progression of ESCC. © 2009 Macmillan Publishers Limited All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/58614
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council Central AllocationHKUST 2/06C
Sun Yat-Sen University 'Hundred Talents Program'85000-3171311
Major State Basic Research Program of China2006CB910104
National Natural Science Foundation of China30772475
Funding Information:

This work was supported by Research Grant Council Central Allocation ( HKUST 2/06C), Sun Yat-Sen University 'Hundred Talents Program' (85000-3171311), a grant from the Major State Basic Research Program of China (2006CB910104) and a grant from the National Natural Science Foundation of China ( 30772475).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorZhu, Cen_HK
dc.contributor.authorQin, YRen_HK
dc.contributor.authorXie, Den_HK
dc.contributor.authorChua, DTTen_HK
dc.contributor.authorFung, JMen_HK
dc.contributor.authorChen, Len_HK
dc.contributor.authorFu, Len_HK
dc.contributor.authorHu, Len_HK
dc.contributor.authorGuan, XYen_HK
dc.date.accessioned2010-05-31T03:33:32Z-
dc.date.available2010-05-31T03:33:32Z-
dc.date.issued2009en_HK
dc.identifier.citationOncogene, 2009, v. 28 n. 31, p. 2821-2828en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58614-
dc.description.abstractDeletion of 3p is one of the most frequent genetic alterations in many tumors, including esophageal squamous cell carcinoma (ESCC). In our recent study, deletion of 3p24 was frequently detected in ESCC and one candidate tumor suppressor gene (TSG), p300/CBP-associated factor (PCAF), was identified within the region. In this study, downregulation of PCAF was detected in 23/40 (57.5%) of primary ESCCs and 4/9 (44.4%) of the ESCC cell lines. A further study found that downregulation of PCAF was also associated with hypermethylation of the promoter region of PCAF gene. Methylation-specific PCR found that promoter methylation was detected in 28/40 (70%) of primary ESCCs and 5/9 (55.6%) of ESCC cell lines. In addition, the expression of PCAF could be reactivated in ESCC cell line KYSE510 after demethylation treatment with 5-aza-dC. Functional studies showed that PCAF was able to suppress tumorigenicity of ESCC cells both in vitro and in vivo, including foci formation, colony formation in soft agar and tumor formation in nude mice. Molecular study found that the tumor suppressive mechanism of PCAF was associated with its role in cell cycle arrest at the G1/S checkpoint by the downregulation of CDK2 and upregulation of p21 waf1/Cip1, Smad4, Rb and p27 Kip1. In conclusion, PCAF might be the target TSG responsible for the 3p24 deletion event, which has an important role in the development and progression of ESCC. © 2009 Macmillan Publishers Limited All rights reserved.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_HK
dc.relation.ispartofOncogeneen_HK
dc.subjectEsophageal squamous cell carcinomaen_HK
dc.subjectLoss of heterozygosityen_HK
dc.subjectMethylationen_HK
dc.subjectPCAFen_HK
dc.subjectTumor suppressor geneen_HK
dc.subject.meshAdulten_HK
dc.subject.meshAgeden_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshApoptosisen_HK
dc.subject.meshBlotting, Westernen_HK
dc.subject.meshCarcinoma, Squamous Cell - genetics - metabolism - pathologyen_HK
dc.subject.meshCell Cycleen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshChromosome Deletionen_HK
dc.subject.meshChromosomes, Human, Pair 3 - geneticsen_HK
dc.subject.meshDNA Methylationen_HK
dc.subject.meshEsophageal Neoplasms - genetics - metabolism - pathologyen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshFlow Cytometryen_HK
dc.subject.meshHumansen_HK
dc.subject.meshImmunohistochemistryen_HK
dc.subject.meshLoss of Heterozygosityen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Nudeen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshNeoplasms, Experimental - genetics - metabolism - pathologyen_HK
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_HK
dc.subject.meshTransplantation, Heterologousen_HK
dc.subject.meshp300-CBP Transcription Factors - genetics - metabolism - physiologyen_HK
dc.titleCharacterization of tumor suppressive function of P300/CBP-associated factor at frequently deleted region 3p24 in esophageal squamous cell carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0950-9232&volume=28&spage=2821&epage=2828&date=2009&atitle=Characterization+of+tumor+suppressive+function+of+P300/CBP-associated+factor+at+frequently+deleted+region+3p24+in+esophageal+squamous+cell+carcinoma.en_HK
dc.identifier.emailChua, DTT: dttchua@hkucc.hku.hken_HK
dc.identifier.emailFu, L: gracelfu@hku.hken_HK
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hken_HK
dc.identifier.authorityChua, DTT=rp00415en_HK
dc.identifier.authorityFu, L=rp01435en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/onc.2009.137en_HK
dc.identifier.pmid19525977-
dc.identifier.scopuseid_2-s2.0-68349125550en_HK
dc.identifier.hkuros157666en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-68349125550&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume28en_HK
dc.identifier.issue31en_HK
dc.identifier.spage2821en_HK
dc.identifier.epage2828en_HK
dc.identifier.isiWOS:000268684400005-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectEsophageal Carcinoma Research Center-
dc.relation.projectEsophageal Carcinoma Research Center-
dc.relation.projectEsophageal Carcinoma Research Center-
dc.relation.projectEsophageal Carcinoma Research Center-
dc.relation.projectEsophageal Carcinoma Research Center-
dc.relation.projectEsophageal Carcinoma Research Center-
dc.identifier.scopusauthoridZhu, C=24466014600en_HK
dc.identifier.scopusauthoridQin, YR=7403100680en_HK
dc.identifier.scopusauthoridXie, D=35070710200en_HK
dc.identifier.scopusauthoridChua, DTT=7006773480en_HK
dc.identifier.scopusauthoridFung, JM=23469161200en_HK
dc.identifier.scopusauthoridChen, L=23569135400en_HK
dc.identifier.scopusauthoridFu, L=22979236700en_HK
dc.identifier.scopusauthoridHu, L=25958137600en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK
dc.identifier.citeulike4918551-

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