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KRAS Activation and over-expression of SIRT1/BCL6 Contributes to the Pathogenesis of Endometriosis and Progesterone Resistance

DC FieldValueLanguage
dc.contributor.author유정윤-
dc.date.accessioned2018-10-10T08:12:04Z-
dc.date.available2018-10-10T08:12:04Z-
dc.date.issued2017-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/163384-
dc.description.abstractEndometriosis is an inflammatory condition that is associated with progesterone resistance and cell proliferation, resulting in pain, infertility and pregnancy loss. We previously demonstrated phosphorylation of STAT3 in eutopic endometrium of infertile women with this disorder leading to over-expression of the oncogene BCL6 and stabilization of hypoxia-induced factor 1 alpha (HIF-1α). Here we report coordinated activation of KRAS and over-expression of Sirtuin 1 (SIRT1), a histone deacetylase and gene silencer, in the eutopic endometrium from women with endometriosis throughout the menstrual cycle. The mice with conditional activation of KRAS in the PGR positive cells reveal an increase of SIRT1 expression in the endometrium compared to control mice. The expression of progesterone receptor target genes including the Indian Hedgehog pathway genes are significantly down-regulated in the mutant mice. SIRT1 co-localizes with BCL6 in the nuclei of affected individuals and both proteins bind to and suppress the promoter of GLI1, a critical mediator of progesterone action in the Indian Hedgehog pathway, by ChIP analysis. In eutopic endometrium, GLI1 expression is reduced in women with endometriosis. Together, these data suggest that KRAS, SIRT1 and BCL6 are coordinately over-expressed in eutopic endometrium of women with endometriosis and likely participate in the pathogenesis of endometriosis.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherNature Publishing Group-
dc.relation.isPartOfSCIENTIFIC REPORTS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleKRAS Activation and over-expression of SIRT1/BCL6 Contributes to the Pathogenesis of Endometriosis and Progesterone Resistance-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Biochemistry & Molecular Biology-
dc.contributor.googleauthorJung-Yoon Yoo-
dc.contributor.googleauthorTae Hoon Kim-
dc.contributor.googleauthorAsgerally T. Fazleabas-
dc.contributor.googleauthorWilder A. Palomino-
dc.contributor.googleauthorSoo Hyun Ahn-
dc.contributor.googleauthorChandrakant Tayade-
dc.contributor.googleauthorDavid P. Schammel-
dc.contributor.googleauthorSteven L. Young-
dc.contributor.googleauthorJae-Wook Jeong-
dc.contributor.googleauthorBruce A. Lessey-
dc.identifier.doi10.1038/s41598-017-04577-w-
dc.contributor.localIdA02502-
dc.relation.journalcodeJ02646-
dc.identifier.eissn2045-2322-
dc.identifier.pmid28754906-
dc.contributor.alternativeNameYoo, Jung Yoon-
dc.contributor.affiliatedAuthorYoo, Jung Yoon-
dc.contributor.affiliatedAuthor유정윤-
dc.citation.volume7-
dc.citation.number1-
dc.citation.startPage6765-
dc.identifier.bibliographicCitationSCIENTIFIC REPORTS, Vol.7(1) : 6765, 2017-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers

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