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dc.contributor.authorMay, Taymaa
dc.contributor.authorYang, Junzheng
dc.contributor.authorShoni, Melina
dc.contributor.authorLiu, Shubai
dc.contributor.authorHe, Housheng
dc.contributor.authorGali, Reddy
dc.contributor.authorNg, Shu-Kay
dc.contributor.authorCrum, Christopher
dc.contributor.authorBerkowitz, Ross S
dc.contributor.authorNg, Shu-Wing
dc.date.accessioned2017-05-03T15:26:18Z
dc.date.available2017-05-03T15:26:18Z
dc.date.issued2013
dc.date.modified2014-01-09T23:19:00Z
dc.identifier.issn1476-5586
dc.identifier.urihttp://hdl.handle.net/10072/55486
dc.description.abstractIntroduction Ovarian cancer is the leading cause of mortality from gynecological malignancy despite advancements in novel therapeutics. We have recently demonstrated that the transcriptional co-repressor C-terminal binding protein 2 (CtBP2) is overexpressed in epithelial ovarian carcinoma. Materials and Methods Reverse-transcribed cDNA from CtBP2 wild-type and knockdown ovarian cancer cell lines was hybridized to Affymetrix Gene 1.0 ST microarrays, and differentially expressed genes were studied. Immunohistochemical analysis of CtBP2 and BRCA1 staining of ovarian tissues was performed. Chromatin immunoprecipitation (ChIP) and luciferase assays were carried out. The effect of the drugs 4-methylthio-2-oxobutyric acid (MTOB) and poly(ADP-ribose) polymerase (PARP) inhibitor Olaparib on CtBP2 wild-type and knockdown cell lines was examined using methylthiazol tetrazolium assays and an xCELLigence System. Results Eighty-five genes involved in DNA repair, mitotic checkpoint, nucleosome assembly, and the BRCA1 network were differentially regulated by CtBP2 expression. ChIP and luciferase reporter assays using a BRCA1 promoter-regulated luciferase construct indicated that the CtBP2 complex binds the BRCA1 promoter and represses BRCA1 transcription. Immunohistochemistry illustrated a significant inverse CtBP2 and BRCA1 expression in a panel of malignant ovarian tumor tissues. The CtBP2 inhibitor MTOB suppressed ovarian cancer cell survival in a CtBP2-dependent manner. Ovarian cancer cells with CtBP2 knockdown did not display increased sensitivity to the PARP inhibitor Olaparib. Conclusion CtBP2 is an ovarian cancer oncogene that may play a significant role in epigenetically silencing BRCA1 function in sporadic epithelial ovarian cancer. CtBP2-specific inhibitors, such as MTOB, may be effective adjunct therapies in the management of patients with CtBP2-positive ovarian carcinoma.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent2372749 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherNeoplasia Press
dc.publisher.placeUnited States
dc.publisher.urihttp://www.neoplasia.com/abstract.php?msid=5816
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom600
dc.relation.ispartofpageto608
dc.relation.ispartofissue6
dc.relation.ispartofjournalNeoPlasia
dc.relation.ispartofvolume15
dc.rights.retentionY
dc.subject.fieldofresearchClinical Sciences
dc.subject.fieldofresearchcode1103
dc.titleBRCA1 expression is epigenetically repressed in sporadic ovarian cancer cells by overexpression of C-Terminal Binding Protein 2
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyright© 2013 Neoplasia Press. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
gro.date.issued2013
gro.hasfulltextFull Text
gro.griffith.authorNg, Shu Kay Angus


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