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Article: Transforming growth factor β1 promotes chromosomal instability in human papillomavirus 16 E6E7-infected cervical epithelial cells

TitleTransforming growth factor β1 promotes chromosomal instability in human papillomavirus 16 E6E7-infected cervical epithelial cells
Authors
Issue Date2008
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2008, v. 68 n. 17, p. 7200-7209 How to Cite?
AbstractUterine cervical cancer, the second most frequently occurring cancer in women worldwide, is tightly associated with the expression of high-risk human papillomavirus [mainly human papillomavirus (HPV)-16 and HPV18] oncogenes E6 and E7 and characteristically exhibits chromosomal instability. However, the mechanisms underlying chromosomal instability in cervical cancer are still not fully understood. In this study, we observed that two of three human cervical epithelial cell lines expressing HPV16 E6E7 became immortalized without extensive chromosomal instability and crisis. The introduction of transforming growth factor (TGF)-β1, a multiple functional cytokine/growth factor, in the culture medium induced crisis, which was associated with massive chromosomal end-to-end fusions and other structural aberrations. The distributions of structural aberrations on individual chromosomes were significantly correlated with the profiles of telomere signal-free ends. The immortalized cells that emerged from the TGF-β1-induced crisis showed multiple clonal structural aberrations that were not observed in cells without TGF-β1 treatment. Overexpression of the catalytic subunit of telomerase (hTERT)abolished the effects of TGF-β1 on chromosomal instability. Interestingly, another HPV16 E6E7-expressing cervical cell line that experienced crisis and telomere dysfunction under ordinary culture condition had a higher level of autocrine TGF-β1 production than the other two crisis-free immortalized cell lines. Blocking the TGF-β1 pathway by an inhibitor of TGF-β1 receptor type I prevented the crisis and telomere-mediated chromosomal instability. In addition, more dramatic telomere shortening was observed in cervical intraepithelial neoplasias having higher expression of TGF-β1 in vivo. These results together suggest an important role of TGF-β1 in the early process of cervical carcinogenesis. ©2008 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/148581
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
Funding AgencyGrant Number
Council of Hong Kong Special Administrative RegionIIKU 7556/06M
University of Hong Kong CRCG200507176189
Funding Information:

Research Grants Council of Hong Kong Special Administrative Region. China. Project, No. IIKU 7556/06M (A.L.M. Cheung); University of Hong Kong 200507176189 (W. Deng and A.L.M. Cheung).

References

 

DC FieldValueLanguage
dc.contributor.authorDeng, Wen_HK
dc.contributor.authorSai, WTen_HK
dc.contributor.authorKwok, YKen_HK
dc.contributor.authorWong, Een_HK
dc.contributor.authorXiao, RHen_HK
dc.contributor.authorLiu, Sen_HK
dc.contributor.authorTsang, CMen_HK
dc.contributor.authorNgan, HYSen_HK
dc.contributor.authorCheung, ANYen_HK
dc.contributor.authorHui, YLen_HK
dc.contributor.authorGuan, XYen_HK
dc.contributor.authorCheung, ALMen_HK
dc.date.accessioned2012-05-29T06:13:52Z-
dc.date.available2012-05-29T06:13:52Z-
dc.date.issued2008en_HK
dc.identifier.citationCancer Research, 2008, v. 68 n. 17, p. 7200-7209en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148581-
dc.description.abstractUterine cervical cancer, the second most frequently occurring cancer in women worldwide, is tightly associated with the expression of high-risk human papillomavirus [mainly human papillomavirus (HPV)-16 and HPV18] oncogenes E6 and E7 and characteristically exhibits chromosomal instability. However, the mechanisms underlying chromosomal instability in cervical cancer are still not fully understood. In this study, we observed that two of three human cervical epithelial cell lines expressing HPV16 E6E7 became immortalized without extensive chromosomal instability and crisis. The introduction of transforming growth factor (TGF)-β1, a multiple functional cytokine/growth factor, in the culture medium induced crisis, which was associated with massive chromosomal end-to-end fusions and other structural aberrations. The distributions of structural aberrations on individual chromosomes were significantly correlated with the profiles of telomere signal-free ends. The immortalized cells that emerged from the TGF-β1-induced crisis showed multiple clonal structural aberrations that were not observed in cells without TGF-β1 treatment. Overexpression of the catalytic subunit of telomerase (hTERT)abolished the effects of TGF-β1 on chromosomal instability. Interestingly, another HPV16 E6E7-expressing cervical cell line that experienced crisis and telomere dysfunction under ordinary culture condition had a higher level of autocrine TGF-β1 production than the other two crisis-free immortalized cell lines. Blocking the TGF-β1 pathway by an inhibitor of TGF-β1 receptor type I prevented the crisis and telomere-mediated chromosomal instability. In addition, more dramatic telomere shortening was observed in cervical intraepithelial neoplasias having higher expression of TGF-β1 in vivo. These results together suggest an important role of TGF-β1 in the early process of cervical carcinogenesis. ©2008 American Association for Cancer Research.en_HK
dc.languageengen_US
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.titleTransforming growth factor β1 promotes chromosomal instability in human papillomavirus 16 E6E7-infected cervical epithelial cellsen_HK
dc.typeArticleen_HK
dc.identifier.emailDeng, W: wdeng@hkucc.hku.hken_HK
dc.identifier.emailSai, WT: gswtsao@hku.hken_HK
dc.identifier.emailLiu, S: stephasl@hku.hken_HK
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_HK
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hken_HK
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hken_HK
dc.identifier.emailCheung, ALM: lmcheung@hku.hken_HK
dc.identifier.authorityDeng, W=rp01640en_HK
dc.identifier.authoritySai, WT=rp00399en_HK
dc.identifier.authorityLiu, S=rp00372en_HK
dc.identifier.authorityNgan, HYS=rp00346en_HK
dc.identifier.authorityCheung, ANY=rp00542en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.identifier.authorityCheung, ALM=rp00332en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1158/0008-5472.CAN-07-6569en_HK
dc.identifier.scopuseid_2-s2.0-52049087107en_HK
dc.identifier.hkuros150983-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-52049087107&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume68en_HK
dc.identifier.issue17en_HK
dc.identifier.spage7200en_HK
dc.identifier.epage7209en_HK
dc.identifier.eissn1538-7445-
dc.identifier.isiWOS:000259080300042-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridDeng, W=7202223673en_HK
dc.identifier.scopusauthoridSai, WT=7102813116en_HK
dc.identifier.scopusauthoridKwok, YK=8247106700en_HK
dc.identifier.scopusauthoridWong, E=23101622300en_HK
dc.identifier.scopusauthoridXiao, RH=24177724000en_HK
dc.identifier.scopusauthoridLiu, S=37102450400en_HK
dc.identifier.scopusauthoridTsang, CM=24831236400en_HK
dc.identifier.scopusauthoridNgan, HYS=34571944100en_HK
dc.identifier.scopusauthoridCheung, ANY=54927484100en_HK
dc.identifier.scopusauthoridHui, YL=7103107517en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK
dc.identifier.scopusauthoridCheung, ALM=7401806497en_HK

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