Differentially androgen-modulated genes in ovarian epithelial cells from BRCA mutation carriers and control patients predict ovarian cancer survival and disease progression

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dc.contributor.authorMotamed-Khorasani, A.en
dc.contributor.authorJurisica, I.en
dc.contributor.authorLetarte, M.en
dc.contributor.authorShaw, P. A.en
dc.contributor.authorParkes, R. K.en
dc.contributor.authorZhang, X.en
dc.contributor.authorEvangelou, A.en
dc.contributor.authorRosen, B.en
dc.contributor.authorMurphy, K. J.en
dc.contributor.authorBrown, T. J.en
dc.date.accessioned2015-11-24T19:24:27Z
dc.date.available2015-11-24T19:24:27Z
dc.identifier.issn0950-9232-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/22479
dc.rightsDefault Licence-
dc.subjectAcetylcholinesterase/genetics/metabolismen
dc.subjectAdulten
dc.subjectAgeden
dc.subjectAged, 80 and overen
dc.subjectAndrogens/*pharmacologyen
dc.subjectBRCA1 Protein/*geneticsen
dc.subjectBasic-Leucine Zipper Transcription Factors/genetics/metabolismen
dc.subjectCarcinoma, Endometrioid/genetics/metabolismen
dc.subjectCarcinoma, Papillary/genetics/metabolismen
dc.subjectCells, Cultureden
dc.subjectCystadenocarcinoma, Serous/genetics/metabolismen
dc.subjectDisease Progressionen
dc.subjectEpithelial Cells/metabolismen
dc.subjectFemaleen
dc.subjectFlow Cytometryen
dc.subjectGene Expression Profilingen
dc.subjectGene Expression Regulation, Neoplasticen
dc.subjectHumansen
dc.subjectImmunoenzyme Techniquesen
dc.subjectLeucine Zippersen
dc.subjectMiddle Ageden
dc.subject*Mutationen
dc.subjectOligonucleotide Array Sequence Analysisen
dc.subjectOvarian Neoplasms/*genetics/metabolism/*mortalityen
dc.subjectOvary/*metabolism/pathologyen
dc.subjectRNA, Messenger/analysis/geneticsen
dc.subjectRNA, Neoplasm/analysisen
dc.subjectReverse Transcriptase Polymerase Chain Reactionen
dc.subjectSurvival Rateen
dc.subjectTissue Array Analysisen
dc.titleDifferentially androgen-modulated genes in ovarian epithelial cells from BRCA mutation carriers and control patients predict ovarian cancer survival and disease progressionen
heal.abstractEpidemiological studies have implicated androgens in the etiology and progression of epithelial ovarian cancer. We previously reported that some androgen responses were dysregulated in malignant ovarian epithelial cells relative to control, non-malignant ovarian surface epithelial (OSE) cells. Moreover, dysregulated androgen responses were observed in OSE cells derived from patients with germline BRCA-1 or -2 mutations (OSEb), which account for the majority of familial ovarian cancer predisposition, and such altered responses may be involved in ovarian carcinogenesis or progression. In the present study, gene expression profiling using cDNA microarrays identified 17 genes differentially expressed in response to continuous androgen exposure in OSEb cells and ovarian cancer cells as compared to OSE cells derived from control patients. A subset of these differentially affected genes was selected and verified by quantitative real-time reverse transcription-polymerase chain reaction. Six of the gene products mapped to the OPHID protein-protein interaction database, and five were networked within two interacting partners. Basic leucine zipper transcription factor 2 (BACH2) and acetylcholinesterase (ACHE), which were upregulated by androgen in OSEb cells relative to OSE cells, were further investigated using an ovarian cancer tissue microarray from a separate set of 149 clinical samples. Both cytoplasmic ACHE and BACH2 immunostaining were significantly increased in ovarian cancer relative to benign cases. High levels of cytoplasmic ACHE staining correlated with decreased survival, whereas nuclear BACH2 staining correlated with decreased time to disease recurrence. The finding that products of genes differentially responsive to androgen in OSEb cells may predict survival and disease progression supports a role for altered androgen effects in ovarian cancer. In addition to BACH2 and ACHE, this study highlights a set of potentially functionally related genes for further investigation in ovarian cancer.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1038/sj.onc.1209773-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/16832351-
heal.identifier.secondaryhttp://www.nature.com/onc/journal/v26/n2/pdf/1209773a.pdf-
heal.journalNameOncogeneen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2007-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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