NBR1 and KIF14 Downstream of the Mammarian Target of Rapamycin Pathway Predict Recurrence in Nonmuscle Invasive Low Grade Urothelial Carcinoma of the Bladder
DC Field | Value | Language |
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dc.contributor.author | Lee, Dong-Gi | - |
dc.contributor.author | Kim, Ha Jeong | - |
dc.contributor.author | Jin, Subin | - |
dc.contributor.author | Kim, Jin Wook | - |
dc.contributor.author | Whang,Young Mi | - |
dc.contributor.author | Lee, Tae-Jin | - |
dc.contributor.author | Chang, In Ho | - |
dc.date.available | 2019-03-08T10:58:09Z | - |
dc.date.issued | 2017 | - |
dc.identifier.issn | 1598-8341 | - |
dc.identifier.issn | 2233-5633 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/5791 | - |
dc.description.abstract | Purpose: The lack of identified mammalian target of rapamycin (mTOR) pathway downstream genes that overcome cross-talk in nonmuscle invasive low grade (LG)-urothelial carcinoma (UC) of the bladder is a clinical limitation in the use of mTOR inhibitor for the treatment of UC.Materials and Methods: Presently, gene expression patterns, gene ontology, and gene clustering by dual (p70S6K and S6K) siRNAs or rapamycin in 253J and TR4 cell lines were investigated by microarray analysis.mTOR/S6K pathway downstream genes suppressed to siRNAs, and rapamycin up-regulated or rapamycin down-regulated genes were identified. The mTOR downstream genes examined using a tissue microarray of 90 nonmuscle invasive LG-UC patients to assess whether any of these genes predicted clinical outcomes. A knockout study evaluated the synergistic effect with rapamycin.Results: In the microarray analysis, mTOR pathway downstream genes selected consisted of 4 rapamycin down-regulated (FOXM1, KIF14, MYBL2, and UHRF1), and 4 rapamycin up-regulated (GPR87, NBR1, VASH1, and PRIMA1). In the tissue microarray, FOXM1, KIF14, and NBR1 were more expressed at T1, and MYBL2, and PRIMA1 were more expressed in tumors exceeding 3 cm. In a multivariate Cox regression model, KIF14 and NBR1 were significant predictors of recurrence in nonmuscle invasive LG-UC of the bladder. In a NBR1 knock out model, rapamycin treatment synergistically inhibited cell viability and colony forming ability compared to rapamycin only.Conclusions: The results implicate KIF14 and NBR1 as mTOR/S6K pathway downstream genes that predict recurrence in nonmuscle invasive LG-UC of the bladder and demonstrate that NBR1 knockout overcomes rapamycin cross-talk. | - |
dc.format.extent | 10 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | 대한비뇨기종양학회 | - |
dc.title | NBR1 and KIF14 Downstream of the Mammarian Target of Rapamycin Pathway Predict Recurrence in Nonmuscle Invasive Low Grade Urothelial Carcinoma of the Bladder | - |
dc.type | Article | - |
dc.identifier.doi | 10.22465/kjuo.2017.15.1.28 | - |
dc.identifier.bibliographicCitation | 대한비뇨기종양학술지, v.15, no.1, pp 28 - 37 | - |
dc.identifier.kciid | ART002217454 | - |
dc.description.isOpenAccess | Y | - |
dc.citation.endPage | 37 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 28 | - |
dc.citation.title | 대한비뇨기종양학술지 | - |
dc.citation.volume | 15 | - |
dc.subject.keywordAuthor | Urinary bladder neoplasms | - |
dc.subject.keywordAuthor | mTOR | - |
dc.subject.keywordAuthor | Biomarkers | - |
dc.subject.keywordAuthor | Microarray analysis | - |
dc.subject.keywordAuthor | Recurrence | - |
dc.description.journalRegisteredClass | kciCandi | - |
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