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15-Deoxy-△12,14-prostaglandin J2 upregulates the expression of 15-hydroxyprostaglandin dehydrogenase through DNA methyltransferase 1 inactivation : 인체 유방암세포에서 15-deoxy-△12,14-prostaglandin J2 의 DNA methyltransferase 1 비활성화를 통한 15-hydroxyprostaglandin dehydrogenase 발현 증가에 대한 기전 연구
DC Field | Value | Language |
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dc.contributor.advisor | 서영준 | - |
dc.contributor.author | 장혜옥 | - |
dc.date.accessioned | 2017-07-19T11:05:01Z | - |
dc.date.available | 2017-07-19T11:05:01Z | - |
dc.date.issued | 2014-02 | - |
dc.identifier.other | 000000016992 | - |
dc.identifier.uri | https://hdl.handle.net/10371/133337 | - |
dc.description | 학위논문 (석사)-- 서울대학교 융합과학기술대학원 : 분자의학 및 바이오제약학과, 2014. 2. 서영준. | - |
dc.description.abstract | 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is the key enzyme that catalyzes the degradation of prostaglandin E2. The expression of 15-PGDH is ubiquitously down-regulated in various cancers, and hence considered as a tumor suppressor. Hypermethylation of CpG islands in the gene promoter region is an important mechanism to silence the expression of tumor suppressor genes and contributes to cancer formation. 15-Deoxy-△12,14-prostaglandin J2 (15d-PGJ2), one of the terminal products of cyclooxygenase-2, has been reported to have anti-inflammatory and anti-carcinogenic activities. The aim of this study is to investigate the effect of 15d-PGJ2 on DNA methylation. In the present study, we demonstrated that 15d-PGJ2 up-regulated 15-PGDH expression by decreasing the level of CpG methylation in 15-PGDH promoter regions in human breast cancer MDA-MB-231 cells. 15d-PGJ2 inhibited the activity of DNA methyltransferase 1 (DNMT1) which is the major enzyme responsible for maintaining DNA methylation. However, 15d-PGJ2 showed no effects on expression of either mRNA or protein of DNMT1. We notably found that 15d-PGJ2 directly interacted with DNMT1, thereby reducing its catalytic activity. However, a non-electrophilic analogue 9,10-dihydro-15d-PGJ2 failed to suppress the methylation of CpG islands present in 15-PGDH promoter, suggesting that the α,β-unsaturated carbonyl group is essential for 15d-PGJ2-mediated inactivation of DNMT1 and subsequent up-regulation of 15-PGDH expression. Chromatin-immunoprecipitation (ChIP) analysis revealed that 15d-PGJ2 significantly attenuated DNMT1 binding to the 15-PGDH promoter regions. Taken together, these findings suggest that 15d-PGJ2 increases 15-PGDH expression by suppressing DNMT1-mediated hypermethylation of 15-PGDH promoter. | - |
dc.description.tableofcontents | TABLE OF CONTENTS
Abstract•• •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• i Table of Contents •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• iii List of Figures ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• iv Introduction •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 1 Materials and Methods •••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 4 Results ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••13 Discussion ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 32 References ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 37 Abstract in Korean •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 41 | - |
dc.format | application/pdf | - |
dc.format.extent | 1106122 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | 15-Deoxy-△12 | - |
dc.subject | 14-prostaglandin J2 | - |
dc.subject | 15-Hydroxyprostaglandin Dehydrogenase | - |
dc.subject | DNA methyltrasferase 1 | - |
dc.subject.ddc | 610 | - |
dc.title | 15-Deoxy-△12,14-prostaglandin J2 upregulates the expression of 15-hydroxyprostaglandin dehydrogenase through DNA methyltransferase 1 inactivation | - |
dc.title.alternative | 인체 유방암세포에서 15-deoxy-△12,14-prostaglandin J2 의 DNA methyltransferase 1 비활성화를 통한 15-hydroxyprostaglandin dehydrogenase 발현 증가에 대한 기전 연구 | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | Hye-Ok Jang | - |
dc.description.degree | Master | - |
dc.citation.pages | iv, 42 | - |
dc.contributor.affiliation | 융합과학기술대학원 분자의학 및 바이오제약학과 | - |
dc.date.awarded | 2014-02 | - |
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