Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/40208
標題: Nuclear expression of dynamin-related protein 1 in lung adenocarcinomas
作者: Chiang, Y.Y.
周寬基
Chen, S.L.
Hsiao, Y.T.
Huang, C.H.
Lin, T.Y.
Chiang, I.P.
Hsu, W.H.
Chow, K.C.
關鍵字: dynamin-related protein 1
nuclear transport
cisplatin resistance
lung
adenocarcinomas
hHR23A
AMPK
dna-damage response
mitochondrial fission
cell-death
hypoxic
conditions
gene-expression
cancer-cells
repair
drp1
apoptosis
pathway
期刊/報告no:: Modern Pathology, Volume 22, Issue 9, Page(s) 1139-1150.
摘要: Dynamin-related protein 1 (DRP1), an 80 kDa GTPase, is involved in mitochondrial fission and anticancer drug-mediated cytotoxicity, which implicate an association with disease progression of cancer. In this study we investigated the prognostic value of DRP1 in lung adenocarcinomas. Using immunohistochemistry, we measured the expression of DRP1 in 227 patients with lung adenocarcinomas. Expression of DRP1 was confirmed by immunoblotting. The correlation between DRP1 expression and clinicopathological parameters was analyzed by statistical analysis. Difference of survivals between different groups was compared by a log-rank test. The results showed that DRP1 expression was detected in 202 patients with lung adenocarcinomas. Among these, nuclear DRP1 (DRP1(nuc)) was detected in 184 patients. A significant difference was found in cumulative survival between patients with high DRP1(nuc) levels and those with DRP1(cyt) levels (P<0.001). In vitro, hypoxia increased DRP1(nuc) levels and cisplatin resistance. Antibodies specific to DRP1 co-precipitated a human homologue of yeast Rad23 protein A (hHR23A) and silencing of hHR23A decreased the nuclear DRP1 level and cisplatin resistance. In conclusion, DRP1(nuc) is highly expressed in lung adenocarcinomas, and correlates with poor prognosis. Nuclear DRP1 may increase drug resistance during hypoxia, and hHR23A is essential for nuclear transportation of DRP1. Our results suggest that other than the protein level alone, intracellular distribution of the protein is critical for determining the protein function in cells. Modern Pathology (2009) 22, 1139-1150; doi: 10.1038/modpathol.2009.83; published online 12 June 2009
URI: http://hdl.handle.net/11455/40208
ISSN: 0893-3952
文章連結: http://dx.doi.org/10.1038/modpathol.2009.83
Appears in Collections:生物醫學研究所

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