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Article: Functional characterization of THY1 as a tumor suppressor gene with antiinvasive activity in nasopharyngeal carcinoma

TitleFunctional characterization of THY1 as a tumor suppressor gene with antiinvasive activity in nasopharyngeal carcinoma
Authors
KeywordsAntiinvasive
Nasopharyngeal carcinoma
Tetracycline-regulated gene expression
THY1
Tumor suppressor gene
Issue Date2010
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, 2010, v. 127 n. 2, p. 304-312 How to Cite?
AbstractTHY1 was previously identified as a candidate tumor suppressor gene (TSG) associated with lymph node metastases in nasopharyngeal carcinoma (NPC) through functional studies. It was identified by oligonucleotide microarray analysis as an interesting differentially expressed gene. However, direct functional evidence is still lacking for THY1 being a TSG in NPC, as in vivo tumorigenicity assays have not been previously reported in our last study of THY1. In this study, a tetracycline-inducible expression vector, pETE-Bsd, was used to obtain stable transfectants of THY1. The stringent in vivo tumorigenicity assay results show that the activation of THY1 suppresses tumor formation of HONE1 cells in nude mice, and the tumor formation ability was restored in the presence of doxycycline (a tetracycline analog), when the gene is shut off. Functional inactivation of this gene is observed in all the tumors derived from the tumorigenic transfectant. The tumor suppressive effect could be repressed by knockdown of THY1 expression in nontumorigenic microcell hybrids. Further studies indicate that expression of THY1 inhibits HONE1 cell growth in vitro by arresting cells in G0/G1 phase. It greatly reduces the ability for anchorage-independent growth. The invasiveness of HONE1 cells was also inhibited by the expression of THY1. These findings suggest that THY1 is a TSG in NPC, which is involved in invasion and shows an association with tumor metastasis. Taken together, THY1 clearly plays an important functional role in tumor suppression in NPC. © 2009 UICC.
Persistent Identifierhttp://hdl.handle.net/10722/65479
ISSN
2015 Impact Factor: 5.531
2015 SCImago Journal Rankings: 2.657
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of the Hong Kong Special Administrative Region, People's Republic of ChinaCA03/04.SC01
Swedish Cancer Society
Swedish Research Council
Swedish Foundation for International Cooperation in Research and Higher Education (STINT)
Swedish Institute
Royal Swedish Academy of Sciences
INTAS
Karolinska Institute
Funding Information:

Grant sponsor: Research Grants Council of the Hong Kong Special Administrative Region, People's Republic of China; Grant number: CA03/04.SC01; Grant sponsors: the Swedish Cancer Society, the Swedish Research Council, the Swedish Foundation for International Cooperation in Research and Higher Education (STINT), the Swedish Institute, the Royal Swedish Academy of Sciences, INTAS, Karolinska Institute

References

 

DC FieldValueLanguage
dc.contributor.authorLung, HLen_HK
dc.contributor.authorCheung, AKLen_HK
dc.contributor.authorCheng, Yen_HK
dc.contributor.authorKwong, FMen_HK
dc.contributor.authorLo, PHYen_HK
dc.contributor.authorLaw, EWLen_HK
dc.contributor.authorChua, Den_HK
dc.contributor.authorZabarovsky, ERen_HK
dc.contributor.authorWang, Nen_HK
dc.contributor.authorTsao, SWen_HK
dc.contributor.authorStanbridge, EJen_HK
dc.contributor.authorLung, MLen_HK
dc.date.accessioned2010-08-10T06:26:24Z-
dc.date.available2010-08-10T06:26:24Z-
dc.date.issued2010en_HK
dc.identifier.citationInternational Journal Of Cancer, 2010, v. 127 n. 2, p. 304-312en_HK
dc.identifier.issn0020-7136en_HK
dc.identifier.urihttp://hdl.handle.net/10722/65479-
dc.description.abstractTHY1 was previously identified as a candidate tumor suppressor gene (TSG) associated with lymph node metastases in nasopharyngeal carcinoma (NPC) through functional studies. It was identified by oligonucleotide microarray analysis as an interesting differentially expressed gene. However, direct functional evidence is still lacking for THY1 being a TSG in NPC, as in vivo tumorigenicity assays have not been previously reported in our last study of THY1. In this study, a tetracycline-inducible expression vector, pETE-Bsd, was used to obtain stable transfectants of THY1. The stringent in vivo tumorigenicity assay results show that the activation of THY1 suppresses tumor formation of HONE1 cells in nude mice, and the tumor formation ability was restored in the presence of doxycycline (a tetracycline analog), when the gene is shut off. Functional inactivation of this gene is observed in all the tumors derived from the tumorigenic transfectant. The tumor suppressive effect could be repressed by knockdown of THY1 expression in nontumorigenic microcell hybrids. Further studies indicate that expression of THY1 inhibits HONE1 cell growth in vitro by arresting cells in G0/G1 phase. It greatly reduces the ability for anchorage-independent growth. The invasiveness of HONE1 cells was also inhibited by the expression of THY1. These findings suggest that THY1 is a TSG in NPC, which is involved in invasion and shows an association with tumor metastasis. Taken together, THY1 clearly plays an important functional role in tumor suppression in NPC. © 2009 UICC.en_HK
dc.languageeng-
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.-
dc.subjectAntiinvasiveen_HK
dc.subjectNasopharyngeal carcinomaen_HK
dc.subjectTetracycline-regulated gene expressionen_HK
dc.subjectTHY1en_HK
dc.subjectTumor suppressor geneen_HK
dc.subject.meshAntigens, Thy-1 - physiology-
dc.subject.meshCell Movement-
dc.subject.meshGene Expression Regulation, Neoplastic - physiology-
dc.subject.meshGenes, Tumor Suppressor - physiology-
dc.subject.meshNasopharyngeal Neoplasms - genetics - metabolism - pathology-
dc.titleFunctional characterization of THY1 as a tumor suppressor gene with antiinvasive activity in nasopharyngeal carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0020-7136&volume=127&issue=2&spage=304&epage=312&date=2009&atitle=Functional+characterization+of+THY1+as+a+tumor+suppressor+gene+with+antiinvasive+activity+in+nasopharyngeal+carcinoma-
dc.identifier.emailLung, HL: hllung2@hku.hken_HK
dc.identifier.emailCheung, AKL: arthurhk@hku.hken_HK
dc.identifier.emailCheng, Y: yuecheng@hku.hken_HK
dc.identifier.emailChua, D: dttchua@hkucc.hku.hken_HK
dc.identifier.emailTsao, SW: gswtsao@hkucc.hku.hken_HK
dc.identifier.emailLung, ML: mlilung@hku.hken_HK
dc.identifier.authorityLung, HL=rp00299en_HK
dc.identifier.authorityCheung, AKL=rp01769en_HK
dc.identifier.authorityCheng, Y=rp01320en_HK
dc.identifier.authorityChua, D=rp00415en_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.identifier.authorityLung, ML=rp00300en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/ijc.25047en_HK
dc.identifier.pmid19921696-
dc.identifier.scopuseid_2-s2.0-77953709847en_HK
dc.identifier.hkuros173235-
dc.identifier.hkuros168362-
dc.identifier.hkuros186156-
dc.identifier.hkuros186345-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77953709847&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume127en_HK
dc.identifier.issue2en_HK
dc.identifier.spage304en_HK
dc.identifier.epage312en_HK
dc.identifier.eissn1097-0215-
dc.identifier.isiWOS:000278919000006-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLung, HL=6603819904en_HK
dc.identifier.scopusauthoridCheung, AKL=8967932600en_HK
dc.identifier.scopusauthoridCheng, Y=36131038300en_HK
dc.identifier.scopusauthoridKwong, FM=8158557800en_HK
dc.identifier.scopusauthoridLo, PHY=36762664000en_HK
dc.identifier.scopusauthoridLaw, EWL=36742183700en_HK
dc.identifier.scopusauthoridChua, D=7006773480en_HK
dc.identifier.scopusauthoridZabarovsky, ER=7007009108en_HK
dc.identifier.scopusauthoridWang, N=7404340716en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK
dc.identifier.scopusauthoridStanbridge, EJ=7103249410en_HK
dc.identifier.scopusauthoridLung, ML=7006411788en_HK

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