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Article: Inactivation of human MAD2b in nasopharyngeal carcinoma cells leads to chemosensitization to DNA-damaging agents

TitleInactivation of human MAD2b in nasopharyngeal carcinoma cells leads to chemosensitization to DNA-damaging agents
Authors
Issue Date2006
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2006, v. 66 n. 8, p. 4357-4367 How to Cite?
AbstractRev7p has been suggested to play an important role in regulating DNA damage response in yeast, and recently, the human homologue (i.e., MAD2B) has been identified, which shares significant homology to the mitotic checkpoint protein MAD2. In this study, we investigated whether MAD2B played a key role in cellular sensitivity to DNA-damaging anticancer drugs by suppressing its expression using RNA interference in nasopharyngeal carcinoma cells. Using colony formation assay, we found that suppression of MAD2B conferred hypersensitivity to a range of DNA-damaging agents, especially DNA cross-linkers, such as cisplatin, and γ-irradiation. This effect was associated with reduced frequencies of spontaneous and drug-induced mutations, elevated phosphorylation of histone H2AX, and markedly increased chromosomal aberrations in response to DNA damage. In addition, there was also a significant decrease in cisplatin-induced sister chromatid exchange rate, a marker for homologous recombination-mediated post-replication repair in MAD2B-depleted cells. These results indicate that MAD2B may be a key factor in regulating cellular response to DNA damage in cancer cells. Our findings reveal a novel strategy for cancer therapy, in which cancer cells are sensitized to DNA-damaging anticancer drugs through inactivation of the MAD2B gene. ©2006 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/67633
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCheung, HWen_HK
dc.contributor.authorChun, ACSen_HK
dc.contributor.authorWang, Qen_HK
dc.contributor.authorDeng, Wen_HK
dc.contributor.authorHu, Len_HK
dc.contributor.authorGuan, XYen_HK
dc.contributor.authorNicholls, JMen_HK
dc.contributor.authorLing, MTen_HK
dc.contributor.authorYong, CWen_HK
dc.contributor.authorSai, WTen_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorWang, Xen_HK
dc.date.accessioned2010-09-06T05:56:52Z-
dc.date.available2010-09-06T05:56:52Z-
dc.date.issued2006en_HK
dc.identifier.citationCancer Research, 2006, v. 66 n. 8, p. 4357-4367en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67633-
dc.description.abstractRev7p has been suggested to play an important role in regulating DNA damage response in yeast, and recently, the human homologue (i.e., MAD2B) has been identified, which shares significant homology to the mitotic checkpoint protein MAD2. In this study, we investigated whether MAD2B played a key role in cellular sensitivity to DNA-damaging anticancer drugs by suppressing its expression using RNA interference in nasopharyngeal carcinoma cells. Using colony formation assay, we found that suppression of MAD2B conferred hypersensitivity to a range of DNA-damaging agents, especially DNA cross-linkers, such as cisplatin, and γ-irradiation. This effect was associated with reduced frequencies of spontaneous and drug-induced mutations, elevated phosphorylation of histone H2AX, and markedly increased chromosomal aberrations in response to DNA damage. In addition, there was also a significant decrease in cisplatin-induced sister chromatid exchange rate, a marker for homologous recombination-mediated post-replication repair in MAD2B-depleted cells. These results indicate that MAD2B may be a key factor in regulating cellular response to DNA damage in cancer cells. Our findings reveal a novel strategy for cancer therapy, in which cancer cells are sensitized to DNA-damaging anticancer drugs through inactivation of the MAD2B gene. ©2006 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.meshCell Line, Tumoren_HK
dc.subject.meshChromatids - genetics - metabolismen_HK
dc.subject.meshDNA Damageen_HK
dc.subject.meshDown-Regulationen_HK
dc.subject.meshDrug Resistance, Neoplasmen_HK
dc.subject.meshHistones - metabolismen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMitosisen_HK
dc.subject.meshNasopharyngeal Neoplasms - drug therapy - genetics - metabolismen_HK
dc.subject.meshPhosphorylationen_HK
dc.subject.meshProteins - antagonists & inhibitors - genetics - metabolismen_HK
dc.subject.meshRNA Interferenceen_HK
dc.subject.meshTransfectionen_HK
dc.titleInactivation of human MAD2b in nasopharyngeal carcinoma cells leads to chemosensitization to DNA-damaging agentsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-5472&volume=66&issue=8&spage=4357&epage=4367&date=2006&atitle=Inactivation+of+human+MAD2B+in+nasopharyngeal+carcinoma+cells+leads+to+chemosensitization+to+DNA-damaging+agentsen_HK
dc.identifier.emailDeng, W: wdeng@hkucc.hku.hken_HK
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hken_HK
dc.identifier.emailNicholls, JM: jmnichol@hkucc.hku.hken_HK
dc.identifier.emailLing, MT: patling@hkucc.hku.hken_HK
dc.identifier.emailYong, CW: ycwong@hkucc.hku.hken_HK
dc.identifier.emailSai, WT: gswtsao@hku.hken_HK
dc.identifier.emailJin, DY: dyjin@hku.hken_HK
dc.identifier.authorityDeng, W=rp01640en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.identifier.authorityNicholls, JM=rp00364en_HK
dc.identifier.authorityLing, MT=rp00449en_HK
dc.identifier.authorityYong, CW=rp00316en_HK
dc.identifier.authoritySai, WT=rp00399en_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/0008-5472.CAN-05-3602en_HK
dc.identifier.pmid16618761-
dc.identifier.scopuseid_2-s2.0-33646240593en_HK
dc.identifier.hkuros115750en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33646240593&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume66en_HK
dc.identifier.issue8en_HK
dc.identifier.spage4357en_HK
dc.identifier.epage4367en_HK
dc.identifier.isiWOS:000236843200052-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridCheung, HW=7201839381en_HK
dc.identifier.scopusauthoridChun, ACS=7003650706en_HK
dc.identifier.scopusauthoridWang, Q=7406910452en_HK
dc.identifier.scopusauthoridDeng, W=7202223673en_HK
dc.identifier.scopusauthoridHu, L=25958137600en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK
dc.identifier.scopusauthoridNicholls, JM=7201463077en_HK
dc.identifier.scopusauthoridLing, MT=7102229780en_HK
dc.identifier.scopusauthoridYong, CW=7403041798en_HK
dc.identifier.scopusauthoridSai, WT=7102813116en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridWang, X=7501854829en_HK

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