Therapeutic Potential of Dickkopf-1 in Wild-Type BRAF Papillary Thyroid Cancer via Regulation of beta-Catenin/E-cadherin Signaling
DC Field | Value | Language |
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dc.contributor.author | Cho, Sun Wook | - |
dc.contributor.author | Kim, Young A. | - |
dc.contributor.author | Sun, Hyun Jin | - |
dc.contributor.author | Ahn, Hwa Young | - |
dc.contributor.author | Lee, Eun Kyung | - |
dc.contributor.author | Yi, Ka Hee | - |
dc.contributor.author | Oh, Byung-Chul | - |
dc.contributor.author | Park, Do Joon | - |
dc.contributor.author | Cho, Bo Youn | - |
dc.contributor.author | Park, Young Joo | - |
dc.date.available | 2019-03-08T21:02:28Z | - |
dc.date.issued | 2014-09 | - |
dc.identifier.issn | 0021-972X | - |
dc.identifier.issn | 1945-7197 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/11880 | - |
dc.description.abstract | Background: Aberrant activation of the Wnt/beta-catenin pathway is a common pathogenesis of various human cancers. We investigated the role of the Wnt inhibitor, Dkk-1, in papillary thyroid cancer (PTC). Methods: Immunohistochemical beta-catenin staining was performed in tissue microarray containing 148 PTCs and five normal thyroid tissues. In vivo effects of Dkk-1 were explored using ectopic tumors with BHP10-3SC cells. Results: In 27 PTC patients, 60% of patients showed beta-catenin up-regulation and Dkk-1 down-regulation in tumor vs normal tissues. Tissue microarray analysis showed that 14 of 148 PTC samples exhibited cytoplasmic-dominant beta-catenin expression compared to membranous-dominant expression in normal tissues. Aberrant beta-catenin expression was significantly correlated with higher rates of the loss of membranous E-cadherin expression and poor disease-free survival than that in the normal membranous expression group over a median follow-up period of 14 years. Implantation of Dkk-1-overexpressing BHP10-3SC cells revealed delayed tumor growth, resulting from the rescue of membranous beta-catenin and E-cadherin expressions. Furthermore, tissue microarray analysis demonstrated that BRAF(WT) patients had higher rates of aberrant expressions of beta-catenin and E-cadherin than BRAF(V600E) patients. Indeed, the inhibitory effects of Dkk-1 on cell survival were more sensitive in BRAF(WT) (BHP10-3SC and TPC-1) than in BRAF(V600E) (SNU-790 and BCPAP) cells. Overexpression of BRAF(V600E) in normal thyroid epithelial (H tori) cells also reduced the effects of Dkk-1 on cell survival. Conclusion: A subset of PTC patients showed aberrant expression of beta-catenin/E-cadherin signaling and poor disease-free survival. Dkk-1 might have a therapeutic role, particularly in BRAF(WT) patients. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | ENDOCRINE SOC | - |
dc.title | Therapeutic Potential of Dickkopf-1 in Wild-Type BRAF Papillary Thyroid Cancer via Regulation of beta-Catenin/E-cadherin Signaling | - |
dc.type | Article | - |
dc.identifier.doi | 10.1210/jc.2013-4467 | - |
dc.identifier.bibliographicCitation | JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v.99, no.9, pp E1641 - E1649 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000342341400006 | - |
dc.identifier.scopusid | 2-s2.0-84907199636 | - |
dc.citation.endPage | E1649 | - |
dc.citation.number | 9 | - |
dc.citation.startPage | E1641 | - |
dc.citation.title | JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | - |
dc.citation.volume | 99 | - |
dc.type.docType | Article | - |
dc.publisher.location | 미국 | - |
dc.subject.keywordPlus | BRAF(V600E) MUTATION | - |
dc.subject.keywordPlus | PROGNOSTIC-FACTORS | - |
dc.subject.keywordPlus | HIGH PREVALENCE | - |
dc.subject.keywordPlus | MELANOMA-CELLS | - |
dc.subject.keywordPlus | CARCINOMA | - |
dc.subject.keywordPlus | LOCALIZATION | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | GENE | - |
dc.relation.journalResearchArea | Endocrinology & Metabolism | - |
dc.relation.journalWebOfScienceCategory | Endocrinology & Metabolism | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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