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Article: Ectopic expression of a COOH-terminal fragment of the human telomerase reverse transcriptase leads to telomere dysfunction and reduction of growth and tumorigenicity in HeLa cells

TitleEctopic expression of a COOH-terminal fragment of the human telomerase reverse transcriptase leads to telomere dysfunction and reduction of growth and tumorigenicity in HeLa cells
Authors
Issue Date2002
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2002, v. 62 n. 11, p. 3226-3232 How to Cite?
AbstractThe COOH-terminus of telomerase reverse transcriptase (hTERT) has been shown to participate in the nuclear translocation of TERT. Here, we constructed plasmids expressing the COOH-terminal M r 27,000 polypeptide of hTERT (hTERTC27) with the telomerase RNA-binding domains and the reverse transcriptase domains deleted. We showed that ectopic overexpression of this polypeptide caused a defect in telomere maintenance in hTERT-positive HeLa cells, which led to senescence-like growth arrest and apoptosis. The hTERTC27 appears to work by inducing telomere dysfunction, exemplified by significantly increased anaphase chromosome end-to-end fusion events in transfected cells. Significantly, it had no effect on the cellular telomerase enzymatic activity or telomere length. The in vivo effect was further demonstrated as HeLa cells stably expressing hTERTC27 have significantly lower growth rate and reduced tumorigenicity in nude mice xenografts. Results from this study revealed an important function for the COOH terminus of hTERT in maintaining the integrity of telomere structure and chromosome ends, as well as in cell senescence and apoptosis. Furthermore, hTERTC27 provides a new strategy for cancer therapy by inducing telomere dysfunction in cancer cells without affecting the telomerase enzymatic activity.
Persistent Identifierhttp://hdl.handle.net/10722/167737
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHuang, JJen_US
dc.contributor.authorLin, MCen_US
dc.contributor.authorBai, YXen_US
dc.contributor.authorJing, DDen_US
dc.contributor.authorWong, BCYen_US
dc.contributor.authorHan, SWen_US
dc.contributor.authorLin, Jen_US
dc.contributor.authorXu, Ben_US
dc.contributor.authorHuang, CFen_US
dc.contributor.authorKung, HFen_US
dc.date.accessioned2012-10-08T03:10:46Z-
dc.date.available2012-10-08T03:10:46Z-
dc.date.issued2002en_US
dc.identifier.citationCancer Research, 2002, v. 62 n. 11, p. 3226-3232en_US
dc.identifier.issn0008-5472en_US
dc.identifier.urihttp://hdl.handle.net/10722/167737-
dc.description.abstractThe COOH-terminus of telomerase reverse transcriptase (hTERT) has been shown to participate in the nuclear translocation of TERT. Here, we constructed plasmids expressing the COOH-terminal M r 27,000 polypeptide of hTERT (hTERTC27) with the telomerase RNA-binding domains and the reverse transcriptase domains deleted. We showed that ectopic overexpression of this polypeptide caused a defect in telomere maintenance in hTERT-positive HeLa cells, which led to senescence-like growth arrest and apoptosis. The hTERTC27 appears to work by inducing telomere dysfunction, exemplified by significantly increased anaphase chromosome end-to-end fusion events in transfected cells. Significantly, it had no effect on the cellular telomerase enzymatic activity or telomere length. The in vivo effect was further demonstrated as HeLa cells stably expressing hTERTC27 have significantly lower growth rate and reduced tumorigenicity in nude mice xenografts. Results from this study revealed an important function for the COOH terminus of hTERT in maintaining the integrity of telomere structure and chromosome ends, as well as in cell senescence and apoptosis. Furthermore, hTERTC27 provides a new strategy for cancer therapy by inducing telomere dysfunction in cancer cells without affecting the telomerase enzymatic activity.en_US
dc.languageengen_US
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_US
dc.relation.ispartofCancer Researchen_US
dc.subject.meshAnimalsen_US
dc.subject.meshApoptosis - Physiologyen_US
dc.subject.meshCell Division - Physiologyen_US
dc.subject.meshDna-Binding Proteinsen_US
dc.subject.meshHela Cellsen_US
dc.subject.meshHumansen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Nudeen_US
dc.subject.meshPeptide Fragments - Biosynthesis - Genetics - Physiologyen_US
dc.subject.meshTelomerase - Biosynthesis - Genetics - Metabolism - Physiologyen_US
dc.subject.meshTelomere - Physiologyen_US
dc.subject.meshTransfectionen_US
dc.subject.meshXenograft Model Antitumor Assaysen_US
dc.titleEctopic expression of a COOH-terminal fragment of the human telomerase reverse transcriptase leads to telomere dysfunction and reduction of growth and tumorigenicity in HeLa cellsen_US
dc.typeArticleen_US
dc.identifier.emailLin, MC:mcllin@hkucc.hku.hken_US
dc.identifier.emailWong, BCY:bcywong@hku.hken_US
dc.identifier.authorityLin, MC=rp00746en_US
dc.identifier.authorityWong, BCY=rp00429en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.pmid12036938-
dc.identifier.scopuseid_2-s2.0-0036606586en_US
dc.identifier.hkuros68770-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036606586&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume62en_US
dc.identifier.issue11en_US
dc.identifier.spage3226en_US
dc.identifier.epage3232en_US
dc.identifier.isiWOS:000176038500037-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridHuang, JJ=7407194640en_US
dc.identifier.scopusauthoridLin, MC=7404816359en_US
dc.identifier.scopusauthoridBai, YX=7402572310en_US
dc.identifier.scopusauthoridJing, DD=15026705900en_US
dc.identifier.scopusauthoridWong, BCY=7402023340en_US
dc.identifier.scopusauthoridHan, SW=7405942704en_US
dc.identifier.scopusauthoridLin, J=24477746000en_US
dc.identifier.scopusauthoridXu, B=55245608200en_US
dc.identifier.scopusauthoridHuang, CF=7406879416en_US
dc.identifier.scopusauthoridKung, HF=7402514190en_US

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