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Article: The cell cycle checkpoint gene Rad9 is a novel oncogene activated by 11q13 amplification and DNA methylation in breast cancer

TitleThe cell cycle checkpoint gene Rad9 is a novel oncogene activated by 11q13 amplification and DNA methylation in breast cancer
Authors
Issue Date2005
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2005, v. 65 n. 19, p. 8646-8654 How to Cite?
AbstractHuman Rad9 (hRad9), a structural homologue of yeast Schizosaccharomyces pombe rad9, is involved in cell cycle checkpoints and apoptosis. hRad9 can serve as a corepressor of androgen receptor in prostate cancer cells, but little is known about its role in the development of breast or other cancers. In the present study, semiquantitative reverse transcription-PCR showed that Rad9 mRNA levels were up-regulated in 52.1% (25 of 48) of breast tumors, and this up-regulation correlated with tumor size (P = 0.037) and local recurrence (P = 0.033). Overexpression of Rad9 mRNA was partly due to an increase in Rad9 gene number as measured by quantitative PCR. In other breast tumors with Rad9 mRNA overexpression but without increase in gene number, there was differential methylation of two putative Sp1/3 binding sites within the first and second introns of the Rad9 gene, which was similarly found in MCF-7 breast cancer cell line with increased Rad9 mRNA. Silencing Rad9 expression by RNA interference in MCF-7 cell line inhibited its proliferation in vitro. Promoter assays indicated that the Sp1/3 site in intron 2 may act as a silencer. In vivo binding of Sp3 to intron 2 was shown by chromatin immunoprecipitation assays. Treatment of MCF-7 cell line with 5′-aza-2′-deoxycytidine reduced Rad9 mRNA expression and also increased binding of Sp3 to the demethylated intron 2 region. Collectively, these findings suggest that Rad9 is a novel oncogene candidate activated by 11q13 amplification and DNA hypermethylation in breast cancer and may play a role in tumor proliferation and local invasion. ©2005 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/77641
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCheng, CKen_HK
dc.contributor.authorChow, LWCen_HK
dc.contributor.authorLoo, WTYen_HK
dc.contributor.authorChan, TKen_HK
dc.contributor.authorChan, Ven_HK
dc.date.accessioned2010-09-06T07:34:07Z-
dc.date.available2010-09-06T07:34:07Z-
dc.date.issued2005en_HK
dc.identifier.citationCancer Research, 2005, v. 65 n. 19, p. 8646-8654en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/77641-
dc.description.abstractHuman Rad9 (hRad9), a structural homologue of yeast Schizosaccharomyces pombe rad9, is involved in cell cycle checkpoints and apoptosis. hRad9 can serve as a corepressor of androgen receptor in prostate cancer cells, but little is known about its role in the development of breast or other cancers. In the present study, semiquantitative reverse transcription-PCR showed that Rad9 mRNA levels were up-regulated in 52.1% (25 of 48) of breast tumors, and this up-regulation correlated with tumor size (P = 0.037) and local recurrence (P = 0.033). Overexpression of Rad9 mRNA was partly due to an increase in Rad9 gene number as measured by quantitative PCR. In other breast tumors with Rad9 mRNA overexpression but without increase in gene number, there was differential methylation of two putative Sp1/3 binding sites within the first and second introns of the Rad9 gene, which was similarly found in MCF-7 breast cancer cell line with increased Rad9 mRNA. Silencing Rad9 expression by RNA interference in MCF-7 cell line inhibited its proliferation in vitro. Promoter assays indicated that the Sp1/3 site in intron 2 may act as a silencer. In vivo binding of Sp3 to intron 2 was shown by chromatin immunoprecipitation assays. Treatment of MCF-7 cell line with 5′-aza-2′-deoxycytidine reduced Rad9 mRNA expression and also increased binding of Sp3 to the demethylated intron 2 region. Collectively, these findings suggest that Rad9 is a novel oncogene candidate activated by 11q13 amplification and DNA hypermethylation in breast cancer and may play a role in tumor proliferation and local invasion. ©2005 American Association for Cancer Research.en_HK
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_HK
dc.relation.ispartofCancer Researchen_HK
dc.subject.meshAzacitidine - analogs & derivatives - pharmacologyen_HK
dc.subject.meshBase Sequenceen_HK
dc.subject.meshBreast Neoplasms - genetics - metabolism - pathologyen_HK
dc.subject.meshBreast Neoplasms, Male - genetics - metabolism - pathologyen_HK
dc.subject.meshCell Cycle Proteins - antagonists & inhibitors - biosynthesis - geneticsen_HK
dc.subject.meshCell Growth Processes - geneticsen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshChromosomes, Human, Pair 11 - geneticsen_HK
dc.subject.meshCyclin D1 - geneticsen_HK
dc.subject.meshDNA Methylationen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGene Amplificationen_HK
dc.subject.meshGene Expression Regulation, Neoplasticen_HK
dc.subject.meshGene Silencingen_HK
dc.subject.meshHumansen_HK
dc.subject.meshIntronsen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshRNA, Messenger - antagonists & inhibitors - biosynthesis - geneticsen_HK
dc.titleThe cell cycle checkpoint gene Rad9 is a novel oncogene activated by 11q13 amplification and DNA methylation in breast canceren_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-5472&volume=65&spage=8646&epage=8654&date=2005&atitle=The+cell+cycle+checkpoint+gene+Rad9+is+a+novel+oncogene+activated+by+11q13+amplification+and+DNA+methylation+in+breast+canceren_HK
dc.identifier.emailChan, V:vnychana@hkucc.hku.hken_HK
dc.identifier.authorityChan, V=rp00320en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/0008-5472.CAN-04-4243en_HK
dc.identifier.pmid16204032-
dc.identifier.scopuseid_2-s2.0-25444478299en_HK
dc.identifier.hkuros109174en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-25444478299&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume65en_HK
dc.identifier.issue19en_HK
dc.identifier.spage8646en_HK
dc.identifier.epage8654en_HK
dc.identifier.isiWOS:000232199400014-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridCheng, CK=7404797040en_HK
dc.identifier.scopusauthoridChow, LWC=7202532995en_HK
dc.identifier.scopusauthoridLoo, WTY=7003567474en_HK
dc.identifier.scopusauthoridChan, TK=7402687762en_HK
dc.identifier.scopusauthoridChan, V=7202654865en_HK

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