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Article: Gonadotropin-releasing hormone promotes ovarian cancer cell invasiveness through c-Jun NH2-terminal kinase-mediated activation of matrix metalloproteinase (MMP)-2 and MMP-9

TitleGonadotropin-releasing hormone promotes ovarian cancer cell invasiveness through c-Jun NH2-terminal kinase-mediated activation of matrix metalloproteinase (MMP)-2 and MMP-9
Authors
Issue Date2006
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2006, v. 66 n. 22, p. 10902-10910 How to Cite?
AbstractGonadotropin-releasing hormone (GnRH) receptor is present in 80% of ovarian cancer, and numerous studies have provided evidence for a role of GnRH in cell proliferation. In this study, the effect of GnRH on the invasion potential of ovarian cancer cells was investigated. In vitro migration and cell invasion assays with the ovarian cancer cell lines Caov-3 and OVCAR-3 revealed the biphasic nature of GnRH; low concentrations of GnRH agonist (GnRHa) increased the cell motility and invasiveness of these cells, but at increased concentrations, the stimulatory effect was insignificant. Reverse transcription-PCR, Western blot, and gelatin zymography showed that the expression of metastasis-related proteinases, matrix metalloproteinase (MMP)-2 and MMP-9, was up-regulated and activated by GnRHa. Moreover, we observed that GnRHa was able to transactivate the MMP-2 and MMP-9 promoters. The invasive/migratory phenotype activated by GnRHa can be blocked by specific inhibitors or neutralizing antibodies to MMP-2 and MMP-9. Knockdown of the GnRH receptor using small interfering RNA significantly inhibited the GnRH-induced MMP activation, invasion, and migration. In addition, we showed that the c-Jun NH2-terminal kinase, but not extracellular signal-regulated kinase 1/2 or p38 mitogen-activated protein kinase, signaling pathway was critical for GnRH-mediated up-regulation of MMP, cell invasion, and motility. These results indicate for the first time an expanded role for GnRH in other aspects of ovarian tumor progression, such as metastasis, via activation of MMP and the subsequent increase in cell migration and invasion. ©2006 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/178971
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCheung, LWTen_US
dc.contributor.authorLeung, PCKen_US
dc.contributor.authorWong, ASTen_US
dc.date.accessioned2012-12-19T09:51:09Z-
dc.date.available2012-12-19T09:51:09Z-
dc.date.issued2006en_US
dc.identifier.citationCancer Research, 2006, v. 66 n. 22, p. 10902-10910en_US
dc.identifier.issn0008-5472en_US
dc.identifier.urihttp://hdl.handle.net/10722/178971-
dc.description.abstractGonadotropin-releasing hormone (GnRH) receptor is present in 80% of ovarian cancer, and numerous studies have provided evidence for a role of GnRH in cell proliferation. In this study, the effect of GnRH on the invasion potential of ovarian cancer cells was investigated. In vitro migration and cell invasion assays with the ovarian cancer cell lines Caov-3 and OVCAR-3 revealed the biphasic nature of GnRH; low concentrations of GnRH agonist (GnRHa) increased the cell motility and invasiveness of these cells, but at increased concentrations, the stimulatory effect was insignificant. Reverse transcription-PCR, Western blot, and gelatin zymography showed that the expression of metastasis-related proteinases, matrix metalloproteinase (MMP)-2 and MMP-9, was up-regulated and activated by GnRHa. Moreover, we observed that GnRHa was able to transactivate the MMP-2 and MMP-9 promoters. The invasive/migratory phenotype activated by GnRHa can be blocked by specific inhibitors or neutralizing antibodies to MMP-2 and MMP-9. Knockdown of the GnRH receptor using small interfering RNA significantly inhibited the GnRH-induced MMP activation, invasion, and migration. In addition, we showed that the c-Jun NH2-terminal kinase, but not extracellular signal-regulated kinase 1/2 or p38 mitogen-activated protein kinase, signaling pathway was critical for GnRH-mediated up-regulation of MMP, cell invasion, and motility. These results indicate for the first time an expanded role for GnRH in other aspects of ovarian tumor progression, such as metastasis, via activation of MMP and the subsequent increase in cell migration and invasion. ©2006 American Association for Cancer Research.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.meshCell Line, Tumoren_US
dc.subject.meshCell Movement - Drug Effects - Physiologyen_US
dc.subject.meshEnzyme Activation - Drug Effectsen_US
dc.subject.meshEnzyme Induction - Drug Effectsen_US
dc.subject.meshFemaleen_US
dc.subject.meshGonadotropin-Releasing Hormone - Pharmacologyen_US
dc.subject.meshHumansen_US
dc.subject.meshJnk Mitogen-Activated Protein Kinases - Metabolismen_US
dc.subject.meshMatrix Metalloproteinase 2 - Antagonists & Inhibitors - Biosynthesis - Genetics - Metabolismen_US
dc.subject.meshMatrix Metalloproteinase 9 - Antagonists & Inhibitors - Biosynthesis - Genetics - Metabolismen_US
dc.subject.meshNeoplasm Invasivenessen_US
dc.subject.meshOvarian Neoplasms - Enzymology - Genetics - Pathologyen_US
dc.subject.meshRna, Messenger - Biosynthesis - Geneticsen_US
dc.subject.meshRna, Small Interfering - Geneticsen_US
dc.subject.meshReceptors, Lhrh - Biosynthesis - Geneticsen_US
dc.subject.meshSignal Transduction - Drug Effectsen_US
dc.subject.meshTransfectionen_US
dc.subject.meshUp-Regulation - Drug Effectsen_US
dc.titleGonadotropin-releasing hormone promotes ovarian cancer cell invasiveness through c-Jun NH2-terminal kinase-mediated activation of matrix metalloproteinase (MMP)-2 and MMP-9en_US
dc.typeArticleen_US
dc.identifier.emailWong, AST: awong1@hkucc.hku.hken_US
dc.identifier.authorityWong, AST=rp00805en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1158/0008-5472.CAN-06-2217en_US
dc.identifier.pmid17108127-
dc.identifier.scopuseid_2-s2.0-33845313655en_US
dc.identifier.hkuros124970-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33845313655&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume66en_US
dc.identifier.issue22en_US
dc.identifier.spage10902en_US
dc.identifier.epage10910en_US
dc.identifier.isiWOS:000242264400034-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridCheung, LWT=14119560800en_US
dc.identifier.scopusauthoridLeung, PCK=12782513900en_US
dc.identifier.scopusauthoridWong, AST=23987963300en_US

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