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Article: Profiling of protein kinases in the neoplastic transformation of human ovarian surface epithelium

TitleProfiling of protein kinases in the neoplastic transformation of human ovarian surface epithelium
Authors
Issue Date2001
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ygyno
Citation
Gynecologic Oncology, 2001, v. 82 n. 2, p. 305-311 How to Cite?
AbstractObjective. The aim of this study was to study the pattern of protein kinase expression in a culture model of epithelial ovarian carcinogenesis. Methods. Cultures of normal human ovarian surface epithelium (OSE), OSE from women with BRCA1 mutations, a cell culture model of preneoplastic (SV40 T-antigen-immortalized, nontumorigenic) and neoplastic (SV40-E-cadherin transfected, tumorigenic) OSE, and three ovarian cancer cell lines were used to represent OSE phenotypes of different genetic backgrounds and at different, progressive stages of neoplastic transformation. The protein kinase network signaling was studied by Western blotting, simultaneously using multiple antibodies for specific protein kinases. Results. High levels of cGMP-dependent protein kinase were found in normal and preneoplastic OSE, but were absent in neoplastic OSE. In contrast, expression of MEK6 was detected exclusively in neoplastic OSE. The expressions of casein kinase II (CK2), p38 mitogen-activated protein kinase (MAPK), cyclin-dependent kinase, and the phosphatidylinositol 3-kinase (PI3K) effectors Akt2 and p70 S6 kinase (S6K) were several-fold higher in neoplastic OSE than in normal OSE, whereas the expressions of the MAPKs extracellular signal-regulated kinases ERK1 and -2 were unchanged. Importantly, constitutive phosphorylation of Akt2 and p70 S6K, as found in neoplastic OSE, was also observed in overtly normal OSE from women with predisposing BRCA1 gene mutations. Conclusions. These data demonstrate that different repertoires of downstream signaling proteins, particularly those of the MEK6-p38 MAPK-CK2 pathway and the PI3K pathway, are correlated with phenotypic manifestations of a cell culture model of OSE at progressive stages in the development of ovarian cancer. Changes in PI3K effectors are already found in overtly normal OSE from women with BRCA1 mutations. © 2001 Academic Press.
Persistent Identifierhttp://hdl.handle.net/10722/178731
ISSN
2015 Impact Factor: 4.198
2015 SCImago Journal Rankings: 2.284
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWong, ASTen_US
dc.contributor.authorKim, SOen_US
dc.contributor.authorLeung, PCKen_US
dc.contributor.authorAuersperg, Nen_US
dc.contributor.authorPelech, SLen_US
dc.date.accessioned2012-12-19T09:49:22Z-
dc.date.available2012-12-19T09:49:22Z-
dc.date.issued2001en_US
dc.identifier.citationGynecologic Oncology, 2001, v. 82 n. 2, p. 305-311en_US
dc.identifier.issn0090-8258en_US
dc.identifier.urihttp://hdl.handle.net/10722/178731-
dc.description.abstractObjective. The aim of this study was to study the pattern of protein kinase expression in a culture model of epithelial ovarian carcinogenesis. Methods. Cultures of normal human ovarian surface epithelium (OSE), OSE from women with BRCA1 mutations, a cell culture model of preneoplastic (SV40 T-antigen-immortalized, nontumorigenic) and neoplastic (SV40-E-cadherin transfected, tumorigenic) OSE, and three ovarian cancer cell lines were used to represent OSE phenotypes of different genetic backgrounds and at different, progressive stages of neoplastic transformation. The protein kinase network signaling was studied by Western blotting, simultaneously using multiple antibodies for specific protein kinases. Results. High levels of cGMP-dependent protein kinase were found in normal and preneoplastic OSE, but were absent in neoplastic OSE. In contrast, expression of MEK6 was detected exclusively in neoplastic OSE. The expressions of casein kinase II (CK2), p38 mitogen-activated protein kinase (MAPK), cyclin-dependent kinase, and the phosphatidylinositol 3-kinase (PI3K) effectors Akt2 and p70 S6 kinase (S6K) were several-fold higher in neoplastic OSE than in normal OSE, whereas the expressions of the MAPKs extracellular signal-regulated kinases ERK1 and -2 were unchanged. Importantly, constitutive phosphorylation of Akt2 and p70 S6K, as found in neoplastic OSE, was also observed in overtly normal OSE from women with predisposing BRCA1 gene mutations. Conclusions. These data demonstrate that different repertoires of downstream signaling proteins, particularly those of the MEK6-p38 MAPK-CK2 pathway and the PI3K pathway, are correlated with phenotypic manifestations of a cell culture model of OSE at progressive stages in the development of ovarian cancer. Changes in PI3K effectors are already found in overtly normal OSE from women with BRCA1 mutations. © 2001 Academic Press.en_US
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ygynoen_US
dc.relation.ispartofGynecologic Oncologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntigens, Polyomavirus Transforming - Genetics - Physiologyen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCadherins - Geneticsen_US
dc.subject.meshCell Transformation, Neoplastic - Metabolismen_US
dc.subject.meshDisease Progressionen_US
dc.subject.meshElectrophoresis, Polyacrylamide Gelen_US
dc.subject.meshEpithelium - Enzymology - Pathologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshGenes, Brca1 - Geneticsen_US
dc.subject.meshHepatocyte Growth Factor - Pharmacologyen_US
dc.subject.meshHumansen_US
dc.subject.meshMiceen_US
dc.subject.meshOvarian Neoplasms - Enzymology - Pathologyen_US
dc.subject.meshOvary - Enzymology - Pathologyen_US
dc.subject.meshPhosphorylationen_US
dc.subject.meshPrecancerous Conditions - Enzymology - Pathologyen_US
dc.subject.meshProtein Kinases - Biosynthesis - Metabolismen_US
dc.subject.meshSignal Transductionen_US
dc.subject.meshSurface Propertiesen_US
dc.subject.meshTransfectionen_US
dc.subject.meshTumor Cells, Cultureden_US
dc.titleProfiling of protein kinases in the neoplastic transformation of human ovarian surface epitheliumen_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.doi10.1006/gyno.2001.6280en_US
dc.identifier.pmid11531284-
dc.identifier.scopuseid_2-s2.0-0034910880en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034910880&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume82en_US
dc.identifier.issue2en_US
dc.identifier.spage305en_US
dc.identifier.epage311en_US
dc.identifier.isiWOS:000170508600015-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridWong, AST=23987963300en_US
dc.identifier.scopusauthoridKim, SO=37109273600en_US
dc.identifier.scopusauthoridLeung, PCK=12782513900en_US
dc.identifier.scopusauthoridAuersperg, N=7006582556en_US
dc.identifier.scopusauthoridPelech, SL=19435899100en_US

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