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Article: The major 8p22 tumor suppressor DLC1 is frequently silenced by methylation in both endemic and sporadic nasopharyngeal, esophageal, and cervical carcinomas, and inhibits tumor cell colony formation

TitleThe major 8p22 tumor suppressor DLC1 is frequently silenced by methylation in both endemic and sporadic nasopharyngeal, esophageal, and cervical carcinomas, and inhibits tumor cell colony formation
Authors
Issue Date2007
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2007, v. 26 n. 6, p. 934-944 How to Cite?
AbstractIdentification of tumor suppressor genes (TSG) silenced by methylation uncovers mechanisms of tumorigenesis and identifies new epigenetic tumor markers for early cancer detection. Both nasopharyngeal carcinoma (NPC) and esophageal carcinoma are major tumors in Southern China and Southeast Asia. Through expression subtraction of NPC, we identified Deleted in Liver Cancer 1 (DLC1)/ARHGAP7 (NM_006094) - an 8p22 TSG as a major downregulated gene. Although expressed in all normal tissues, DLC1 was silenced or downregulated in 11/12 (91%) NPC, 6/15 (40%) esophageal, 5/8 (63%) cervical and 3/9 (33%) breast carcinoma cell lines. No genetic deletion of DLC1 was detected in NPC although a hemizygous deletion at 8p22-11 was found by 1-Mb array-CGH in some cell lines. We then located the functional DLC1 promoter by 5′-RACE and promoter activity assays. This promoter was frequently methylated in all downregulated cell lines and in a large collection of primary tumors including 89% (64/72) NPC (endemic and sporadic types), 51% (48/94) esophageal, 87% (7/8) cervical and 36% (5/14) breast carcinomas, but seldom in paired surgical marginal tissues and not in any normal epithelial tissue. The transcriptional silencing of DLC1 could be reversed by 5-aza-2′-deoxycytidine or genetic double knock-out of DNMT1 and DNMT3B. Furthermore, ectopic expression of DLC1 in NPC and esophageal carcinoma cells strongly inhibited their colony formation. We thus found frequent epigenetic silencing of DLC1 in NPC, esophageal and cervical carcinomas, and a high correlation of methylation with its downregulation, suggesting a predominant role of epigenetic inactivation. DLC1 appears to be a major TSG implicated in the pathogenesis of these tumors, and should be further tested as a molecular biomarker in patients with these cancers. © 2007 Nature Publishing Group All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/88329
ISSN
2014 Impact Factor: 8.459
2014 SCImago Journal Rankings: 3.643
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorSeng, TJen_HK
dc.contributor.authorLow, JSWen_HK
dc.contributor.authorLi, Hen_HK
dc.contributor.authorCui, Yen_HK
dc.contributor.authorGoh, HKen_HK
dc.contributor.authorWong, MLYen_HK
dc.contributor.authorSrivastava, Gen_HK
dc.contributor.authorSidransky, Den_HK
dc.contributor.authorCalifano, Jen_HK
dc.contributor.authorSteenbergen, RDMen_HK
dc.contributor.authorRha, SYen_HK
dc.contributor.authorTan, Jen_HK
dc.contributor.authorHsieh, WSen_HK
dc.contributor.authorAmbinder, RFen_HK
dc.contributor.authorLin, Xen_HK
dc.contributor.authorChan, ATCen_HK
dc.contributor.authorTao, Qen_HK
dc.date.accessioned2010-09-06T09:41:57Z-
dc.date.available2010-09-06T09:41:57Z-
dc.date.issued2007en_HK
dc.identifier.citationOncogene, 2007, v. 26 n. 6, p. 934-944en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88329-
dc.description.abstractIdentification of tumor suppressor genes (TSG) silenced by methylation uncovers mechanisms of tumorigenesis and identifies new epigenetic tumor markers for early cancer detection. Both nasopharyngeal carcinoma (NPC) and esophageal carcinoma are major tumors in Southern China and Southeast Asia. Through expression subtraction of NPC, we identified Deleted in Liver Cancer 1 (DLC1)/ARHGAP7 (NM_006094) - an 8p22 TSG as a major downregulated gene. Although expressed in all normal tissues, DLC1 was silenced or downregulated in 11/12 (91%) NPC, 6/15 (40%) esophageal, 5/8 (63%) cervical and 3/9 (33%) breast carcinoma cell lines. No genetic deletion of DLC1 was detected in NPC although a hemizygous deletion at 8p22-11 was found by 1-Mb array-CGH in some cell lines. We then located the functional DLC1 promoter by 5′-RACE and promoter activity assays. This promoter was frequently methylated in all downregulated cell lines and in a large collection of primary tumors including 89% (64/72) NPC (endemic and sporadic types), 51% (48/94) esophageal, 87% (7/8) cervical and 36% (5/14) breast carcinomas, but seldom in paired surgical marginal tissues and not in any normal epithelial tissue. The transcriptional silencing of DLC1 could be reversed by 5-aza-2′-deoxycytidine or genetic double knock-out of DNMT1 and DNMT3B. Furthermore, ectopic expression of DLC1 in NPC and esophageal carcinoma cells strongly inhibited their colony formation. We thus found frequent epigenetic silencing of DLC1 in NPC, esophageal and cervical carcinomas, and a high correlation of methylation with its downregulation, suggesting a predominant role of epigenetic inactivation. DLC1 appears to be a major TSG implicated in the pathogenesis of these tumors, and should be further tested as a molecular biomarker in patients with these cancers. © 2007 Nature Publishing Group 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.subject.meshBase Sequenceen_HK
dc.subject.meshCell Lineen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshCell Proliferationen_HK
dc.subject.meshChromosomes, Human, Pair 8 - geneticsen_HK
dc.subject.meshDNA Methylationen_HK
dc.subject.meshEsophageal Neoplasms - genetics - metabolismen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGTPase-Activating Proteinsen_HK
dc.subject.meshGene Expression Regulation, Neoplasticen_HK
dc.subject.meshGene Silencingen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshNasopharyngeal Neoplasms - genetics - metabolism - pathologyen_HK
dc.subject.meshPromoter Regions, Genetic - geneticsen_HK
dc.subject.meshTumor Suppressor Proteins - genetics - metabolismen_HK
dc.subject.meshUterine Cervical Neoplasms - genetics - metabolismen_HK
dc.titleThe major 8p22 tumor suppressor DLC1 is frequently silenced by methylation in both endemic and sporadic nasopharyngeal, esophageal, and cervical carcinomas, and inhibits tumor cell colony formationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0950-9232&volume=26&issue=6&spage=934&epage=44&date=2007&atitle=The+major+8p22+tumor+suppressor+DLC1+is+frequently+silenced+by+methylation+in+both+endemic+and+sporadic+nasopharyngeal,+esophageal,+and+cervical+carcinomas,+and+inhibits+tumor+cell+colony+formationen_HK
dc.identifier.emailSrivastava, G:gopesh@pathology.hku.hken_HK
dc.identifier.authoritySrivastava, G=rp00365en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/sj.onc.1209839en_HK
dc.identifier.pmid16862168en_HK
dc.identifier.scopuseid_2-s2.0-33846941189en_HK
dc.identifier.hkuros132803en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33846941189&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume26en_HK
dc.identifier.issue6en_HK
dc.identifier.spage934en_HK
dc.identifier.epage944en_HK
dc.identifier.isiWOS:000244063800013-
dc.publisher.placeUnited Kingdomen_HK
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dc.identifier.citeulike771102-

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