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Radiosensitizing effect of PSMC5, a 19S proteasome ATPase, in H460 lung cancer cells

Title
Radiosensitizing effect of PSMC5, a 19S proteasome ATPase, in H460 lung cancer cells
Author
이수재
Keywords
Akt-Mdm2 pathway; H460 cancer cells; PSMC5; p21; Radiosensitivity biomarker
Issue Date
2016-01
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Citation
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v. 469, NO 1, Page. 94-100
Abstract
The function of PSMC5 (proteasome 26S subunit, ATPase 5) in tumors, particularly with respect to cancer radioresistance, is not known. Here, we identified PSMC5 as a novel radiosensitivity biomarker, demonstrating that radiosensitive H460 cells were converted to a radioresistance phenotype by PSMC5 depletion. Exposure of H460 cells to radiation induced a marked accumulation of cell death-promoting reactive oxygen species, but this effect was blocked in radiation-treated H460 PSMC5-knockdown cells through downregulation of the p53-p21 pathway. Interestingly, PSMC5 depletion in H460 cells enhanced both AKT activation and MDM2 transcription, thereby promoting the degradation of p53 and p21 proteins. Furthermore, specific inhibition of AKT with triciribine or knockdown of MDM2 with small interfering RNA largely restored p21 expression in PSMC5-knockdown H460 cells. Our data suggest that PSMC5 facilitates the damaging effects of radiation in radiation-responsive H460 cancer cells and therefore may serve as a prognostic indicator for radiotherapy and molecular targeted therapy in lung cancer patients. (C) 2015 The Authors. Published by Elsevier Inc.
URI
http://www.sciencedirect.com/science/article/pii/S0006291X15309463?via%3Dihubhttp://hdl.handle.net/20.500.11754/31693
ISSN
0006-291X; 1090-2104
DOI
10.1016/j.bbrc.2015.11.077
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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