BRCA1 185delAG Mutation Enhances Interleukin-1𝛽 Expression in Ovarian Surface Epithelial Cells

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dc.contributor.authorWoolery, Kamisha T.
dc.contributor.authorMohamed, Mai
dc.contributor.authorLinger, Rebecca J.
dc.contributor.authorDobrinski, Kimberly P.
dc.contributor.authorRoman, Jesse
dc.contributor.authorKruk, Patricia A.
dc.date.accessioned2019-11-13T16:24:06Z
dc.date.available2019-11-13T16:24:06Z
dc.date.issued2015-06-17
dc.descriptionCopyright © 2015 Kamisha T. Woolery et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.descriptionFinal Published Version
dc.description.abstractFamilial history remains the strongest risk factor for developing ovarian cancer (OC) and is associated with germline BRCA1 mutations, such as the 185delAG founder mutation. We sought to determine whether normal human ovarian surface epithelial (OSE) cells expressing the BRCA1 185delAG mutant, BRAT, could promote an inflammatory phenotype by investigating its impact on expression of the proinflammatory cytokine, Interleukin-1𝛽 (IL-1𝛽). Cultured OSE cells with and without BRAT were analyzed for differential target gene expression by real-time PCR, western blot, ELISA, luciferase reporter, and siRNA assays.We found that BRAT cells expressed increased cellular and secreted levels of active IL-1𝛽. BRAT-expressing OSE cells exhibited 3-fold enhanced IL- 1𝛽 mRNA expression, transcriptionally regulated, in part, through CREB sites within the (−1800) to (−900) region of its promoter. In addition to transcriptional regulation, BRAT-mediated IL-1𝛽 expression appears dualistic through enhanced inflammasomemediated caspase-1 cleavage and activation of IL-1𝛽. Further investigation is warranted to elucidate the molecularmechanism(s) of BRAT-mediated IL-1𝛽 expression since increased IL-1𝛽 expression may represent an early step contributing to OC.en_US
dc.identifier.citationWoolery KT, Mohamed M, Linger RJ, Dobrinski KP, Roman J, Kruk PA. BRCA1 185delAG Mutation Enhances Interleukin-1β Expression in Ovarian Surface Epithelial Cells. Biomed Res Int. 2015;2015:652017. doi:10.1155/2015/652017en_US
dc.identifier.doihttp://dx.doi.org/10.1155/2015/652017
dc.identifier.issn2314-6141
dc.identifier.otherdoi:10.1155/2015/652017
dc.identifier.urihttp://dx.doi.org/10.1155/2015/652017
dc.language.isoen_USen_US
dc.publisherBioMed Research International, Hindawi Publishing Corporationen_US
dc.subjectOvarian canceren_US
dc.subjectBRCA genesen_US
dc.subjectEpithelial cells
dc.subjectInterleukin-1
dc.subjectGene Expression Regulation
dc.subjectCytokines
dc.subjectInflammasomes
dc.titleBRCA1 185delAG Mutation Enhances Interleukin-1𝛽 Expression in Ovarian Surface Epithelial Cellsen_US
dc.typeArticleen_US

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2015 CNHS Faculty Publications