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A selective cyclin-dependent kinase 4, 6 dual inhibitor, Ribociclib (LEE011) inhibits cell proliferation and induces apoptosis in aggressive thyroid cancer

DC FieldValueLanguage
dc.contributor.author구철룡-
dc.contributor.author이은직-
dc.contributor.author조윤희-
dc.contributor.author이우경-
dc.date.accessioned2018-08-28T17:01:27Z-
dc.date.available2018-08-28T17:01:27Z-
dc.date.issued2018-
dc.identifier.issn0304-3835-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/162176-
dc.description.abstractThe RB-E2F1 pathway is an important mechanism of cell-cycle control, and deregulation of this pathway is one of the key factors contributing to tumorigenesis. Cyclin-dependent kinases (CDKs) and Cyclin D have been known to increase in aggressive thyroid cancer. However, there has been no study to investigate effects of a selective CDK 4/6 inhibitor, Ribociclib (LEE011), in thyroid cancer. Performing Western blotting, we found that RB phosphorylation and the expression of Cyclin D are significantly higher in papillary thyroid cancer (PTC) cell lines as well as anaplastic thyroid cancer (ATC) cell lines, compared with normal thyroid cell line and follicular thyroid cancer cell line. LEE011 dose-dependently inhibited RB phosphorylation and also decreased the expressions of its target genes such as FOXM1, Cyclin A1, and Myc in ATC. Furthermore, LEE011 induced cell cycle arrest in G0-G1 phase and cell apoptosis, and inhibited cell proliferation in ATC. Consistently, oral administration of LEE011 to ATC xenograft models strongly inhibited tumor growth with decreased expressions of pRB, pAKT and Ki-67, and also significantly increased tumor cell apoptosis. Taken together, our data support the rationale for clinical development of the CDK4/6 inhibitor as a therapy for patients with aggressive thyroid cancer.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherElsevier Science Ireland-
dc.relation.isPartOfCancer Letters-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleA selective cyclin-dependent kinase 4, 6 dual inhibitor, Ribociclib (LEE011) inhibits cell proliferation and induces apoptosis in aggressive thyroid cancer-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Internal Medicine-
dc.contributor.googleauthorHyun Joo Lee-
dc.contributor.googleauthorWoo Kyung Lee-
dc.contributor.googleauthorChan Woo Kang-
dc.contributor.googleauthorCheol Ryong Ku-
dc.contributor.googleauthorYoon Hee Cho-
dc.contributor.googleauthorEun Jig Lee-
dc.identifier.doi10.1016/j.canlet.2017.12.037-
dc.contributor.localIdA00201-
dc.contributor.localIdA03050-
dc.contributor.localIdA03878-
dc.contributor.localIdA02991-
dc.relation.journalcodeJ00448-
dc.identifier.eissn1872-7980-
dc.identifier.pmid29306020-
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S0304383518300107-
dc.subject.keywordCDK4-
dc.subject.keywordCDK6-
dc.subject.keywordLEE011-
dc.subject.keywordRetinoblastoma protein (RB)-
dc.subject.keywordThyroid cancer-
dc.contributor.alternativeNameKu, Cheol Ryong-
dc.contributor.alternativeNameLee, Eun Jig-
dc.contributor.alternativeNameCho, Yoon Hee-
dc.contributor.affiliatedAuthorKu, Cheol Ryong-
dc.contributor.affiliatedAuthorLee, Eun Jig-
dc.contributor.affiliatedAuthorCho, Yoon Hee-
dc.citation.volume417-
dc.citation.startPage131-
dc.citation.endPage140-
dc.identifier.bibliographicCitationCancer Letters, Vol.417 : 131-140, 2018-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Institute of Endocrinology (내분비연구소) > 1. Journal Papers

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