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Article: Gonadotropins regulate N-cadherin-mediated human ovarian surface epithelial cell survival at both post-translational and transcriptional levels through a cyclic AMP/protein kinase a pathway

TitleGonadotropins regulate N-cadherin-mediated human ovarian surface epithelial cell survival at both post-translational and transcriptional levels through a cyclic AMP/protein kinase a pathway
Authors
Issue Date2005
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 2005, v. 280 n. 15, p. 15438-15448 How to Cite?
AbstractGonadotropins are the major regulators of ovarian function and may be involved in the etiology of ovarian cancer. In this study, we report a new mechanism whereby gonadotropins regulate the survival of human ovarian surface epithelium (OSE), the tissue of origin of epithelial ovarian carcinomas. Our results indicate that disruption of N-cadherin-mediated cell-cell adhesion is an important molecular event in the apoptosis of human OSE. Treatment with surge serum concentrations of gonadotropins reduced the amount of N-cadherin with a concomitant induction of apoptosis, and this effect was mediated by a cAMP/protein kinase A pathway but not the ERK1/2 and protein kinase C cascades. We further demonstrated that activation of the gonadotropins/ cAMP signaling pathway in human OSE led to a rapid down-regulation of N-cadherin protein level followed by a reduction at the level of N-cadherin mRNA, indicating that expression of N-cadherin was regulated by post-translational and transcriptional mechanisms. The former mechanism was mediated by increased turnover of N-cadherin protein and could be reversed by inhibition of proteasomal or matrix metalloproteinase (MMP-2) activity. On the other hand, at the transcriptional level, the addition of actinomycin D abolished the cAMP-mediated decrease in N-cadherin mRNA but did not change its stability. Inhibition of protein kinase A or expressing a dominant negative mutant of cAMP-response element-binding protein blocked this decrease of N-cadherin mRNA. Together, the combined operation of post-translational and transcriptional mechanisms suggests that regulation of N-cadherin is a crucial event and emphasizes the important role that N-cadherin has in controlling the survival capability of human OSE. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/84925
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYuen, LPen_HK
dc.contributor.authorAuersperg, Nen_HK
dc.contributor.authorWong, ASTen_HK
dc.date.accessioned2010-09-06T08:58:43Z-
dc.date.available2010-09-06T08:58:43Z-
dc.date.issued2005en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2005, v. 280 n. 15, p. 15438-15448en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/84925-
dc.description.abstractGonadotropins are the major regulators of ovarian function and may be involved in the etiology of ovarian cancer. In this study, we report a new mechanism whereby gonadotropins regulate the survival of human ovarian surface epithelium (OSE), the tissue of origin of epithelial ovarian carcinomas. Our results indicate that disruption of N-cadherin-mediated cell-cell adhesion is an important molecular event in the apoptosis of human OSE. Treatment with surge serum concentrations of gonadotropins reduced the amount of N-cadherin with a concomitant induction of apoptosis, and this effect was mediated by a cAMP/protein kinase A pathway but not the ERK1/2 and protein kinase C cascades. We further demonstrated that activation of the gonadotropins/ cAMP signaling pathway in human OSE led to a rapid down-regulation of N-cadherin protein level followed by a reduction at the level of N-cadherin mRNA, indicating that expression of N-cadherin was regulated by post-translational and transcriptional mechanisms. The former mechanism was mediated by increased turnover of N-cadherin protein and could be reversed by inhibition of proteasomal or matrix metalloproteinase (MMP-2) activity. On the other hand, at the transcriptional level, the addition of actinomycin D abolished the cAMP-mediated decrease in N-cadherin mRNA but did not change its stability. Inhibition of protein kinase A or expressing a dominant negative mutant of cAMP-response element-binding protein blocked this decrease of N-cadherin mRNA. Together, the combined operation of post-translational and transcriptional mechanisms suggests that regulation of N-cadherin is a crucial event and emphasizes the important role that N-cadherin has in controlling the survival capability of human OSE. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.titleGonadotropins regulate N-cadherin-mediated human ovarian surface epithelial cell survival at both post-translational and transcriptional levels through a cyclic AMP/protein kinase a pathwayen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9258&volume=280&spage=15438&epage=15448&date=2005&atitle=Gonadotropins+Regulate+N-cadherin-mediated+Human+Ovarian+Surface+Epithelial+Cell+Survival+at+Both+Post-translational+and+Transcriptional+Levels+through+a+Cyclic+AMP/Protein+Kinase+A+Pathwayen_HK
dc.identifier.emailWong, AST: awong1@hkucc.hku.hken_HK
dc.identifier.authorityWong, AST=rp00805en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1074/jbc.M410766200en_HK
dc.identifier.pmid15701645-
dc.identifier.scopuseid_2-s2.0-17644369682en_HK
dc.identifier.hkuros101946en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-17644369682&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume280en_HK
dc.identifier.issue15en_HK
dc.identifier.spage15438en_HK
dc.identifier.epage15448en_HK
dc.identifier.isiWOS:000228236800131-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridYuen, LP=15081685200en_HK
dc.identifier.scopusauthoridAuersperg, N=7006582556en_HK
dc.identifier.scopusauthoridWong, AST=23987963300en_HK

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