Links for fulltext
     (May Require Subscription)
Supplementary

Article: Chromosome 14 transfer and functional studies identify a candidate tumor suppressor gene, Mirror image polydactyly 1, in nasopharyngeal carcinoma

TitleChromosome 14 transfer and functional studies identify a candidate tumor suppressor gene, Mirror image polydactyly 1, in nasopharyngeal carcinoma
Authors
KeywordsCell cycle arrest
Microcell-mediated chromosome transfer
MIPOL1
Promoter hypermethylation
Issue Date2009
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2009, v. 106 n. 34, p. 14478-14483 How to Cite?
AbstractChromosome 14 allelic loss is common in nasopharyngeal carcinoma (NPC) and may reflect essential tumor suppressor gene loss in tumorigenesis. An intact chromosome 14 was transferred to an NPC cell line using a microcell-mediated chromosome transfer approach. Microcell hybrids (MCHs) containing intact exogenously transferred chromosome 14 were tumor suppressive in athymic mice, demonstrating that intact chromosome 14 NPC MCHs are able to suppress tumor growth in mice. Comparative analysis of these MCHs and their derived tumor segregants identified 4 commonly eliminated tumor-suppressive CRs. Here we provide functional evidence that a gene, Mirror-Image POLydactyly 1 (MIPOL1), which maps within a single 14q13.1-13.3 CR and that hitherto has been reported to be associated only with a developmental disorder, specifically suppresses in vivo tumor formation. MIPOL1 gene expression is down-regulated in all NPC cell lines and in ≈63% of NPC tumors via promoter hypermethylation and allelic loss. SLC25A21 and FOXA1, 2 neighboring genes mapping to this region, did not show this frequent down-regulated gene expression or promoter hypermethylation, precluding possible global methylation effects and providing further evidence that MIPOL1 plays a unique role in NPC. The protein localizes mainly to the nucleus. Re-expression of MIPOL1 in the stable transfectants induces cell cycle arrest. MIPOL1 tumor suppression is related to up-regulation of the p21(WAF1/CIP1) and p27(KIP1) protein pathways. This study provides compelling evidence that chromosome 14 harbors tumor suppressor genes associated with NPC and that a candidate gene, MIPOL1, is associated with tumor development.
Persistent Identifierhttp://hdl.handle.net/10722/135079
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of the Hong Kong Special Administrative Region, People's Republic of China661507
Swedish Cancer Society
Swedish Research Council
Swedish Institute
Royal Swedish Academy of Sciences
Karolinska Institute
Funding Information:

Financial support was provided by the Research Grants Council of the Hong Kong Special Administrative Region, People's Republic of China, Grant 661507 to M. L. L. and by the Swedish Cancer Society, the Swedish Research Council, Swedish Institute, Royal Swedish Academy of Sciences, and Karolinska Institute to E.R.Z.

References

 

DC FieldValueLanguage
dc.contributor.authorCheung, AKLen_HK
dc.contributor.authorLung, HLen_HK
dc.contributor.authorKo, JMYen_HK
dc.contributor.authorCheng, Yen_HK
dc.contributor.authorStanbridge, EJen_HK
dc.contributor.authorZabarovsky, ERen_HK
dc.contributor.authorNicholls, JMen_HK
dc.contributor.authorChua, Den_HK
dc.contributor.authorTsao, SWen_HK
dc.contributor.authorGuan, XYen_HK
dc.contributor.authorLung, MLen_HK
dc.date.accessioned2011-07-27T01:27:43Z-
dc.date.available2011-07-27T01:27:43Z-
dc.date.issued2009en_HK
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2009, v. 106 n. 34, p. 14478-14483en_HK
dc.identifier.issn0027-8424en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135079-
dc.description.abstractChromosome 14 allelic loss is common in nasopharyngeal carcinoma (NPC) and may reflect essential tumor suppressor gene loss in tumorigenesis. An intact chromosome 14 was transferred to an NPC cell line using a microcell-mediated chromosome transfer approach. Microcell hybrids (MCHs) containing intact exogenously transferred chromosome 14 were tumor suppressive in athymic mice, demonstrating that intact chromosome 14 NPC MCHs are able to suppress tumor growth in mice. Comparative analysis of these MCHs and their derived tumor segregants identified 4 commonly eliminated tumor-suppressive CRs. Here we provide functional evidence that a gene, Mirror-Image POLydactyly 1 (MIPOL1), which maps within a single 14q13.1-13.3 CR and that hitherto has been reported to be associated only with a developmental disorder, specifically suppresses in vivo tumor formation. MIPOL1 gene expression is down-regulated in all NPC cell lines and in ≈63% of NPC tumors via promoter hypermethylation and allelic loss. SLC25A21 and FOXA1, 2 neighboring genes mapping to this region, did not show this frequent down-regulated gene expression or promoter hypermethylation, precluding possible global methylation effects and providing further evidence that MIPOL1 plays a unique role in NPC. The protein localizes mainly to the nucleus. Re-expression of MIPOL1 in the stable transfectants induces cell cycle arrest. MIPOL1 tumor suppression is related to up-regulation of the p21(WAF1/CIP1) and p27(KIP1) protein pathways. This study provides compelling evidence that chromosome 14 harbors tumor suppressor genes associated with NPC and that a candidate gene, MIPOL1, is associated with tumor development.en_HK
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_HK
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_HK
dc.subjectCell cycle arresten_HK
dc.subjectMicrocell-mediated chromosome transferen_HK
dc.subjectMIPOL1en_HK
dc.subjectPromoter hypermethylationen_HK
dc.subject.meshChromosomes, Human, Pair 14 - genetics-
dc.subject.meshCell Cycle-
dc.subject.meshNasopharyngeal Neoplasms - genetics - metabolism - pathology-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshTumor Suppressor Proteins - genetics - metabolism-
dc.titleChromosome 14 transfer and functional studies identify a candidate tumor suppressor gene, Mirror image polydactyly 1, in nasopharyngeal carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0027-8424&volume=106&issue=34&spage=14478&epage=14483&date=2009&atitle=Chromosome+14+transfer+and+functional+studies+identify+a+candidate+tumor+suppressor+gene,+mirror+image+polydactyly+1,+in+nasopharyngeal+carcinomaen_US
dc.identifier.emailCheung, AKL: arthurhk@hku.hken_HK
dc.identifier.emailLung, HL: hllung2@hku.hken_HK
dc.identifier.emailCheng, Y: yuecheng@hku.hken_HK
dc.identifier.emailNicholls, JM: jmnichol@hkucc.hku.hken_HK
dc.identifier.emailChua, D: dttchua@hkucc.hku.hken_HK
dc.identifier.emailTsao, SW: gswtsao@hkucc.hku.hken_HK
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hken_HK
dc.identifier.emailLung, ML: mlilung@hku.hken_HK
dc.identifier.authorityCheung, AKL=rp01769en_HK
dc.identifier.authorityLung, HL=rp00299en_HK
dc.identifier.authorityCheng, Y=rp01320en_HK
dc.identifier.authorityNicholls, JM=rp00364en_HK
dc.identifier.authorityChua, D=rp00415en_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.identifier.authorityLung, ML=rp00300en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.0900198106en_HK
dc.identifier.pmid19667180-
dc.identifier.pmcidPMC2732794-
dc.identifier.scopuseid_2-s2.0-70149086514en_HK
dc.identifier.hkuros186158en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-70149086514&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume106en_HK
dc.identifier.issue34en_HK
dc.identifier.spage14478en_HK
dc.identifier.epage14483en_HK
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000269295100057-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridCheung, AKL=8967932600en_HK
dc.identifier.scopusauthoridLung, HL=6603819904en_HK
dc.identifier.scopusauthoridKo, JMY=35725559400en_HK
dc.identifier.scopusauthoridCheng, Y=36131038300en_HK
dc.identifier.scopusauthoridStanbridge, EJ=7103249410en_HK
dc.identifier.scopusauthoridZabarovsky, ER=7007009108en_HK
dc.identifier.scopusauthoridNicholls, JM=7201463077en_HK
dc.identifier.scopusauthoridChua, D=7006773480en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK
dc.identifier.scopusauthoridLung, ML=7006411788en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats