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Article: Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase

TitleMolecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase
Authors
KeywordsImmortalization
Nasopharyngeal carcinoma
p16
RASSF1A
Telomerase
Issue Date2006
PublisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
Citation
International Journal Of Cancer, 2006, v. 119 n. 7, p. 1567-1576 How to Cite?
AbstractNasopharyngeal carcinoma (NPC) is a common disease in Hong Kong and southern provinces of China. EBV infection is believed to play a critical role in the development of NPC, Previous studies on the transformation mechanism of EBV genes were mostly performed in either NPC or nonnasopharyngeal epithelial cells which may not be representative of premalignant nasopharyngeal epithelial cells. Establishment of a representative cell system would greatly facilitate the elucidation of the role of EBV infection in the development of NPC. Using telomerase alone, we were able to establish an immortalized nasopharyngeal epithelial cell line from primary nonmalignant nasopharyngeal biopsies. The telomerase-immortalized nasopharyngeal epithelial cells are largely diploid in karyotype. Interestingly, this newly immortalized nasopharyngeal epithelial cell line, referred as NP460hTert, harbors genetic alterations previously identified in premalignant and malignant nasopharyngeal epithelial cells. These include inactivation of p16 by homozygous deletion of the p16 INK4A locus and downregulation of RASSF1A expression. The deletion of the p16 INK4A locus appears to be the most crucial event for the immortalization of nasopharyngeal epithelial cells by telomerase and precedes RASSF1A downregulation. In addition, detailed analysis of the cytogenetic changes by conventional cytogenetics, spectral karyotyping (SKY) and array-based CGH revealed a gain of a 17q21-q25 fragment on 11p15 chromosome in all NP460hTert cells which occurred before deletion of the p16 INK4A locus. Gain of 17q has been previously reported in NPC. In addition, activation of NF-κB was observed in immortalized NP460hTert cells at the later population doublings, and may play a role in the survival of immortalized NP epithelial cells. Id1 which is commonly expressed in various human cancers, including NPC, was also upregulated in the immortalized NP460hTert cells. Thus, the establishment of an immortalized nasopharyngeal epithelial cell line harboring common genetic alterations present in premalignant and cancerous nasopharyngeal epithelial cells may provide a valuable cell system to examine for early events involved in NPC carcinogenesis, particularly in elucidating the role of EBV infection in NPC development. © 2006 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/67342
ISSN
2015 Impact Factor: 5.531
2015 SCImago Journal Rankings: 2.657
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, HMen_HK
dc.contributor.authorMan, Cen_HK
dc.contributor.authorJin, Yen_HK
dc.contributor.authorDeng, Wen_HK
dc.contributor.authorYip, YLen_HK
dc.contributor.authorFeng, HCen_HK
dc.contributor.authorCheung, YCen_HK
dc.contributor.authorLo, KWen_HK
dc.contributor.authorMeltzer, PSen_HK
dc.contributor.authorWu, ZGen_HK
dc.contributor.authorKwong, YLen_HK
dc.contributor.authorYuen, APWen_HK
dc.contributor.authorTsao, SWen_HK
dc.date.accessioned2010-09-06T05:54:16Z-
dc.date.available2010-09-06T05:54:16Z-
dc.date.issued2006en_HK
dc.identifier.citationInternational Journal Of Cancer, 2006, v. 119 n. 7, p. 1567-1576en_HK
dc.identifier.issn0020-7136en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67342-
dc.description.abstractNasopharyngeal carcinoma (NPC) is a common disease in Hong Kong and southern provinces of China. EBV infection is believed to play a critical role in the development of NPC, Previous studies on the transformation mechanism of EBV genes were mostly performed in either NPC or nonnasopharyngeal epithelial cells which may not be representative of premalignant nasopharyngeal epithelial cells. Establishment of a representative cell system would greatly facilitate the elucidation of the role of EBV infection in the development of NPC. Using telomerase alone, we were able to establish an immortalized nasopharyngeal epithelial cell line from primary nonmalignant nasopharyngeal biopsies. The telomerase-immortalized nasopharyngeal epithelial cells are largely diploid in karyotype. Interestingly, this newly immortalized nasopharyngeal epithelial cell line, referred as NP460hTert, harbors genetic alterations previously identified in premalignant and malignant nasopharyngeal epithelial cells. These include inactivation of p16 by homozygous deletion of the p16 INK4A locus and downregulation of RASSF1A expression. The deletion of the p16 INK4A locus appears to be the most crucial event for the immortalization of nasopharyngeal epithelial cells by telomerase and precedes RASSF1A downregulation. In addition, detailed analysis of the cytogenetic changes by conventional cytogenetics, spectral karyotyping (SKY) and array-based CGH revealed a gain of a 17q21-q25 fragment on 11p15 chromosome in all NP460hTert cells which occurred before deletion of the p16 INK4A locus. Gain of 17q has been previously reported in NPC. In addition, activation of NF-κB was observed in immortalized NP460hTert cells at the later population doublings, and may play a role in the survival of immortalized NP epithelial cells. Id1 which is commonly expressed in various human cancers, including NPC, was also upregulated in the immortalized NP460hTert cells. Thus, the establishment of an immortalized nasopharyngeal epithelial cell line harboring common genetic alterations present in premalignant and cancerous nasopharyngeal epithelial cells may provide a valuable cell system to examine for early events involved in NPC carcinogenesis, particularly in elucidating the role of EBV infection in NPC development. © 2006 Wiley-Liss, Inc.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/homeen_HK
dc.relation.ispartofInternational Journal of Canceren_HK
dc.rightsInternational Journal of Cancer. Copyright © John Wiley & Sons, Inc.en_HK
dc.subjectImmortalizationen_HK
dc.subjectNasopharyngeal carcinomaen_HK
dc.subjectp16en_HK
dc.subjectRASSF1Aen_HK
dc.subjectTelomeraseen_HK
dc.subject.meshCell Proliferationen_HK
dc.subject.meshCell Shapeen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshCyclin-Dependent Kinase Inhibitor p16 - genetics - metabolismen_HK
dc.subject.meshEpithelial Cells - cytology - metabolismen_HK
dc.subject.meshGene Expression Regulationen_HK
dc.subject.meshHumansen_HK
dc.subject.meshKaryotypingen_HK
dc.subject.meshNF-kappa B - metabolismen_HK
dc.subject.meshNasopharynx - cytology - metabolismen_HK
dc.subject.meshTelomerase - genetics - metabolismen_HK
dc.titleMolecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomeraseen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0020-7136&volume=119&spage=1567&epage=1576&date=2006&atitle=Molecular+and+cytogenetic+changes+involved+in+the+immortalization+of+nasopharyngeal+epithelial+cells+by+telomeraseen_HK
dc.identifier.emailDeng, W: wdeng@hkucc.hku.hken_HK
dc.identifier.emailKwong, YL: ylkwong@hku.hken_HK
dc.identifier.emailTsao, SW: gswtsao@hku.hken_HK
dc.identifier.authorityDeng, W=rp01640en_HK
dc.identifier.authorityKwong, YL=rp00358en_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/ijc.22032en_HK
dc.identifier.pmid16688717-
dc.identifier.scopuseid_2-s2.0-33747502096en_HK
dc.identifier.hkuros124539en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33747502096&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume119en_HK
dc.identifier.issue7en_HK
dc.identifier.spage1567en_HK
dc.identifier.epage1576en_HK
dc.identifier.isiWOS:000240046000008-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLi, HM=8312261000en_HK
dc.identifier.scopusauthoridMan, C=7005722377en_HK
dc.identifier.scopusauthoridJin, Y=7404457413en_HK
dc.identifier.scopusauthoridDeng, W=7202223673en_HK
dc.identifier.scopusauthoridYip, YL=7005596403en_HK
dc.identifier.scopusauthoridFeng, HC=7401736336en_HK
dc.identifier.scopusauthoridCheung, YC=7202111087en_HK
dc.identifier.scopusauthoridLo, KW=7402101603en_HK
dc.identifier.scopusauthoridMeltzer, PS=7102464641en_HK
dc.identifier.scopusauthoridWu, ZG=8218909600en_HK
dc.identifier.scopusauthoridKwong, YL=7102818954en_HK
dc.identifier.scopusauthoridYuen, APW=7006290111en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK

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