Publications
Detailed Information
BRCA2 결손 마우스 유래 3-D 췌장 오거노이드의 염색체 불안정성 분석
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 이현숙 | - |
dc.contributor.author | 김현종 | - |
dc.date.accessioned | 2017-07-19T09:09:48Z | - |
dc.date.available | 2019-11-06 | - |
dc.date.issued | 2016-08 | - |
dc.identifier.other | 000000137430 | - |
dc.identifier.uri | https://hdl.handle.net/10371/131614 | - |
dc.description | 학위논문 (석사)-- 서울대학교 대학원 : 생명과학부, 2016. 8. 이현숙. | - |
dc.description.abstract | Pancreatic cancer remains to be one of the most lethal diseases despite
extensive researches. While essential genes responsible for driving pancreatic cancer were revealed, such as K-Ras or Brca2, molecular mechanism to drive pancreatic cancer is to be elucidated. To unveil molecular mechanism about how Brca2 deficiency is related to the development of pancreatic cancer, I have utilized mouse models and 3-D pancreatic organoid culture throughout this study. Brca2 is tumor-suppressor gene that functions in DNA repair, telomere homeostasis and mitotic checkpoint. During mitosis, it mediates the acetylation of BubR1 with PCAF, thus reinforces spindle assembly checkpoint and prevents chromosome instability. In this study, BubR1K243R/+ acetylation deficient mouse model were crossed with K-RasG12D/+ | - |
dc.description.abstract | Pdx1-CRE
mouse, to assess how chromosome instability can affect the development of pancreatic cancer. Surprisingly, BubR1K243R/+ | - |
dc.description.abstract | K-RasG12D/+ | - |
dc.description.abstract | Pdx1-CRE mice
exhibited expedited tumor growth with shortened life span compared to KRasG12D/+ | - |
dc.description.abstract | Pdx1-CRE mice. Analysis of mitotic progression with Mouse
embryonic fibroblast implied that mitotic progression was aberrated in the existence of BubR1 acetylation deficiency and oncogenic K-Ras mutation. As well-known tumor-suppressor gene, Brca2 mutation is the highest risk factor of familiar pancreatic cancer and also frequently found in spontaneous pancreatic as well. In order to assess how Brca2 depletion can influence on the integrity of telomere in the context of pancreatic ductal epithelium, I have utilized 3-D organoid culture from Brca2 f11/f11 | - |
dc.description.abstract | mTerc-/- mouse model. Unlike
other genotypes, Brca2 f11/f11 | - |
dc.description.abstract | mTerc-/- showed higher rate of telomere fragility,
heterogeneity of length with increased aneuploidy rate. Lastly, I have established pancreatic cancer organoid culture method from patient-derived biopsy sample. This method is envisioned to be the most faithful avatar that reflects individual cancers. A tiny tissue from Endoscopic Ultrasound (EUS)-guided Fine-needle Biopsy (FNB) could be successfully generate pancreatic ductal epithelium, presumably from pancreatic ductal adenocarcinoma and normal ductal tissue. This methodology will be utilized to analyze the patterns of chromosome instability including telomere instability to scrutinize the molecular mechanism of human pancreatic cancer development. | - |
dc.description.tableofcontents | I. Introduction 1
I-1. Maintenance of chromosome instability by mitotic function of Brca2 1 I- 2. Telomere maintenance by Brca2 and induction of Alternative lengthening of telomere by Brca2 depletion 4 I-3. 3-D organoid culture as a model to study in vivo organ biology 7 II. MATERIALS AND METHODS 10 II-1. Maintenance of mouse models and genotyping 10 II-2. Mouse Embryonic Fibroblast culture 11 III-3. 3-D organoid culture from mouse and human biopsy 11 III-4. 2-D and 3-D immunofluorescence assay 13 III-5. Chromosome orientation Fluorescence in situ hybridization (CO-FISH) 14 III. RESULTS 15 III-1. Generation and cooperative tumorigenecity of BubR1K243R/+ | - |
dc.description.tableofcontents | K-RasG12D/+ | - |
dc.description.tableofcontents | Pdx1-CRE mouse 15
III-2. Synergistic mitotic aberration in BubR1K243R/+ | - |
dc.description.tableofcontents | K-RasG12D/+ MEFs 19
III-3. Establishment of mouse pancreatic organoid 23 III-4. Depletion of Brca2 impedes the growth of pancreatic organoid 26 III-5. Depletion of Brca2 can diminish telomere integrity in pancreatic organoid 29 III-6. Establishment of patient-derived pancreatic organoid 33 IV. DISCUSSION 36 V. REFERENCES 39 국문 초록 41 | - |
dc.format | application/pdf | - |
dc.format.extent | 1450617 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | pancreatic cancer | - |
dc.subject | 3-D organoid | - |
dc.subject | BRCA2 | - |
dc.subject | K-ras | - |
dc.subject | chromosome instability | - |
dc.subject | spindle assembly checkpoint | - |
dc.subject.ddc | 570 | - |
dc.title | BRCA2 결손 마우스 유래 3-D 췌장 오거노이드의 염색체 불안정성 분석 | - |
dc.type | Thesis | - |
dc.description.degree | Master | - |
dc.citation.pages | 42 | - |
dc.contributor.affiliation | 자연과학대학 생명과학부 | - |
dc.date.awarded | 2016-08 | - |
- Appears in Collections:
- Files in This Item:
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.