Publications
Detailed Information
Pathogenetic role of Wnt signaling pathway and the function of Dickkopf-1 in thyroid cancers
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 박영주 | - |
dc.contributor.author | 이은정 | - |
dc.date.accessioned | 2017-07-14T01:22:55Z | - |
dc.date.available | 2017-07-14T01:22:55Z | - |
dc.date.issued | 2013-02 | - |
dc.identifier.other | 000000009988 | - |
dc.identifier.uri | https://hdl.handle.net/10371/121897 | - |
dc.description | 학위논문 (박사)-- 서울대학교 대학원 : 의학과 분자유전체의학 전공, 2013. 2. 박영주. | - |
dc.description.abstract | Wnt/beta-catenin signaling plays a role in tumorigenesis of human papillary thyroid cancer (PTC). Dickkopf (Dkk) -1 is a known inhibitor of Wnt/beta-catenin signaling, the therapeutic potential of which is undetermined. In this study, we investigated the therapeutic potential of Dkk-1 in human PTC.
In order to evaluate the clinical significance of Wnt/beta-catenin pathway, we investigated the expression of Wnt in relation to downstream molecules including beta-catenin, cyclin D1, E-cadherin in papillary thyroid cancer. In addition we investigated the anti-tumoral effect of Dkk-1 on two different PTC cell lines, in vitro, to determine the therapeutic potential of Dkk-1 in PTC. A paired comparison between human PTC and normal thyroid tissues from PTC patients revealed that Wnt3 gene expression and total beta-catenin proteins were up-regulated in human PTC tissues. Tissue microarray data revealed that 9.5% of PTC and 100.0% of anaplastic thyroid cancer had aberrant cytoplasmic staining of beta-catenin, while membranous staining was found in all normal tissue. Aberrant locations of beta-catenin in PTC tissues were correlated with the loss of membranous E-cadherin expression. Dkk-1 treatment inhibited PTC cell survival via a pro-apoptotic action. Dkk-1 reversed the aberrant expression of beta-catenin from nucleus to membrane and inhibited basal levels of TCF/LEF dependent transcriptional activities. Furthermore, Dkk-1 inhibited cell viability in dose dependent manners and adenoviral transduction of constitutively active beta-catenin blocked these effects, suggesting that an anti-tumoral effect of Dkk-1 is mediated by Wnt/beta-catenin signaling. In addition, Dkk-1 also recovered the loss of membranous E-cadherin expression with consequent inhibition of cell migration and invasion in both cell lines. Our results suggest that Dkk-1 inhibited human PTC survival and migration by regulating Wnt/beta-catenin signaling and E-cadherin expression. Thus, the interruption of this signaling may therapeutically be useful in thyroid cancer. | - |
dc.description.tableofcontents | Abstract
Contents List of Tables List of Figures List of abberiviations and symbols Introduction Materials and Methods Results Discussion References 국문초록 | - |
dc.format | application/pdf | - |
dc.format.extent | 1305253 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | Dkk-1 | - |
dc.subject | Wnt | - |
dc.subject | beta-catenin | - |
dc.subject | E-cadherin | - |
dc.subject | thyroid cancer | - |
dc.subject.ddc | 610 | - |
dc.title | Pathogenetic role of Wnt signaling pathway and the function of Dickkopf-1 in thyroid cancers | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | LEE EUN JUNG | - |
dc.description.degree | Doctor | - |
dc.citation.pages | ix,48 | - |
dc.contributor.affiliation | 의과대학 의학과 | - |
dc.date.awarded | 2013-02 | - |
- 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.