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Article: Latent membrane protein 1 suppresses RASSF1A expression, disrupts microtubule structures and induces chromosomal aberrations in human epithelial cells

TitleLatent membrane protein 1 suppresses RASSF1A expression, disrupts microtubule structures and induces chromosomal aberrations in human epithelial cells
Authors
KeywordsEpstein-Barr virus
LMP1
Microtubules
Nasopharyngeal epithelial cells
NF-κB
RASSF1A
Issue Date2007
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2007, v. 26 n. 21, p. 3069-3080 How to Cite?
AbstractEpstein-Barr virus (EBV) infection is closely associated with nasopharyngeal carcinoma (NPC) and can be detected in early premalignant lesions of nasopharyngeal epithelium. The latent membrane protein 1 (LMP1) is an oncoprotein encoded by the EBV and is believed to play a role in transforming premalignant nasopharyngeal epithelial cells into cancer cells. RASSF1A is a tumor-suppressor gene commonly inactivated in many types of human cancer including NPC. In this study, we report a novel function of LMP1, in down-regulating RASSF1A expression in human epithelial cells. Downregulation of RASSF1A expression by LMP1 is dependent on the activation of intracellular signaling of NF-κB involving the C-terminal activating regions (CTARs) of LMP1. LMP1 expression also suppresses the transcriptional activity of the RASSF1A core promoter. RASSF1A stabilizes microtubules and regulates mitotic events. Aberrant mitotic spindles and chromosome aberrations are reported phenotypes in RASSF1A inactivated cells. In this study, we observed that LMP1 expression in human epithelial cells could induce aberrant mitotic spindles, disorganized interphase microtubules and aneuploidy. LMP1 expression could also suppress microtubule dynamics as exemplified by tracking movements of the growing tips of microtubules in live cells by transfecting EGFP-tagged EB1 into cells. The aberrant mitotic spindles and interphase microtubule organization induced by LMP1 could be rescued by transfecting RASSF1A expression plasmid into cells. Downregulation of RASSF1A expression by LMP1 may facilitate its role in transformation of premalignant nasopharyngeal epithelial cells into cancer cells. © 2007 Nature Publishing Group All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/67398
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMan, Cen_HK
dc.contributor.authorRosa, Jen_HK
dc.contributor.authorLee, LTOen_HK
dc.contributor.authorLee, VHYen_HK
dc.contributor.authorChow, BKCen_HK
dc.contributor.authorLo, KWen_HK
dc.contributor.authorDoxsey, Sen_HK
dc.contributor.authorWu, ZGen_HK
dc.contributor.authorKwong, YLen_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorCheung, ALMen_HK
dc.contributor.authorTsao, SWen_HK
dc.date.accessioned2010-09-06T05:54:47Z-
dc.date.available2010-09-06T05:54:47Z-
dc.date.issued2007en_HK
dc.identifier.citationOncogene, 2007, v. 26 n. 21, p. 3069-3080en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67398-
dc.description.abstractEpstein-Barr virus (EBV) infection is closely associated with nasopharyngeal carcinoma (NPC) and can be detected in early premalignant lesions of nasopharyngeal epithelium. The latent membrane protein 1 (LMP1) is an oncoprotein encoded by the EBV and is believed to play a role in transforming premalignant nasopharyngeal epithelial cells into cancer cells. RASSF1A is a tumor-suppressor gene commonly inactivated in many types of human cancer including NPC. In this study, we report a novel function of LMP1, in down-regulating RASSF1A expression in human epithelial cells. Downregulation of RASSF1A expression by LMP1 is dependent on the activation of intracellular signaling of NF-κB involving the C-terminal activating regions (CTARs) of LMP1. LMP1 expression also suppresses the transcriptional activity of the RASSF1A core promoter. RASSF1A stabilizes microtubules and regulates mitotic events. Aberrant mitotic spindles and chromosome aberrations are reported phenotypes in RASSF1A inactivated cells. In this study, we observed that LMP1 expression in human epithelial cells could induce aberrant mitotic spindles, disorganized interphase microtubules and aneuploidy. LMP1 expression could also suppress microtubule dynamics as exemplified by tracking movements of the growing tips of microtubules in live cells by transfecting EGFP-tagged EB1 into cells. The aberrant mitotic spindles and interphase microtubule organization induced by LMP1 could be rescued by transfecting RASSF1A expression plasmid into cells. Downregulation of RASSF1A expression by LMP1 may facilitate its role in transformation of premalignant nasopharyngeal epithelial cells into cancer cells. © 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.subjectEpstein-Barr virusen_HK
dc.subjectLMP1en_HK
dc.subjectMicrotubulesen_HK
dc.subjectNasopharyngeal epithelial cellsen_HK
dc.subjectNF-κBen_HK
dc.subjectRASSF1Aen_HK
dc.subject.meshChromosome Aberrations-
dc.subject.meshDown-Regulation - genetics-
dc.subject.meshEpithelial Cells - metabolism - pathology-
dc.subject.meshMicrotubules - metabolism - pathology-
dc.subject.meshTumor Suppressor Proteins - antagonists and inhibitors - biosynthesis - genetics-
dc.titleLatent membrane protein 1 suppresses RASSF1A expression, disrupts microtubule structures and induces chromosomal aberrations in human epithelial cellsen_HK
dc.typeArticleen_HK
dc.identifier.emailChow, BKC: bkcc@hku.hken_HK
dc.identifier.emailKwong, YL: ylkwong@hku.hken_HK
dc.identifier.emailJin, DY: dyjin@hku.hken_HK
dc.identifier.emailCheung, ALM: lmcheung@hku.hken_HK
dc.identifier.emailTsao, SW: gswtsao@hku.hken_HK
dc.identifier.authorityChow, BKC=rp00681en_HK
dc.identifier.authorityKwong, YL=rp00358en_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.identifier.authorityCheung, ALM=rp00332en_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1038/sj.onc.1210106en_HK
dc.identifier.pmid17099724-
dc.identifier.scopuseid_2-s2.0-34248368436en_HK
dc.identifier.hkuros140821en_HK
dc.identifier.hkuros125958-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34248368436&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume26en_HK
dc.identifier.issue21en_HK
dc.identifier.spage3069en_HK
dc.identifier.epage3080en_HK
dc.identifier.eissn1476-5594-
dc.identifier.isiWOS:000246395400012-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridMan, C=7005722377en_HK
dc.identifier.scopusauthoridRosa, J=8758103700en_HK
dc.identifier.scopusauthoridLee, LTO=47161324000en_HK
dc.identifier.scopusauthoridLee, VHY=14050662700en_HK
dc.identifier.scopusauthoridChow, BKC=7102826193en_HK
dc.identifier.scopusauthoridLo, KW=17344013500en_HK
dc.identifier.scopusauthoridDoxsey, S=7004246781en_HK
dc.identifier.scopusauthoridWu, ZG=8218909600en_HK
dc.identifier.scopusauthoridKwong, YL=7102818954en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridCheung, ALM=7401806497en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK
dc.identifier.citeulike942472-

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