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Downregulation of ERK2 is essential for the inhibition of radiation-induced cell death in HSP25 overexpressed L929 cells.

Authors
 H N Cho  ;  Y J Lee  ;  C K Cho  ;  S J Lee  ;  Y-S Lee 
Citation
 CELL DEATH AND DIFFERENTIATION, Vol.9(4) : 448-456, 2002 
Journal Title
CELL DEATH AND DIFFERENTIATION
ISSN
 1350-9047 
Issue Date
2002
MeSH
Animals ; Apoptosis*/radiation effects ; CellLine ; Down-Regulation* ; Enzyme Inhibitors/pharmacology ; Flavonoids/pharmacology ; Gene Expression ; Heat-Shock Proteins* ; Mice ; Mitogen-Activated Protein Kinase 1/antagonists & inhibitors ; Mitogen-Activated Protein Kinase 1/metabolism* ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinases/antagonists & inhibitors ; Mitogen-Activated Protein Kinases/metabolism ; Neoplasm Proteins/antagonists & inhibitors ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism* ; Radiation Tolerance ; Transfection
Keywords
HSP25 ; Inhibition of cell death ; apoptosis ; cell growth ; ERK2
Abstract
We previously reported that overexpression of HSP25 delayed cell growth, increased the level of p21(waf), reduced the levels of cyclin D1, cyclin A and cdc2, and induced radioresistance in L929 cells. In this study, we demonstrated that HSP25 induced-radioresistance was abolished by transfection with plasmids containing antisense hsp25 cDNA. Extracellular regulated kinase (ERK) and MAP kinase/ERK kinase (MEK) expressions as well as their activation (phospho-forms) were inhibited by hsp25 overexpression. Furthermore, when control vector transfected cells were treated with PD98059, MEK inhibitor, they became resistant to radiation, suggesting that inhibition of ERK1/2 activities was essential for radioresistance in L929 cells. To confirm the relationship between ERK1/2 and hsp25-mediated radioresistance, ERK1 or ERK2 cDNA was transiently transfected into the hsp25 overexpressed cells and their radioresistance was examined. HSP25-mediated radioresistance was abolished by overexpression of ERK2, but not by overexpression of ERK1. Alteration of cell cycle distribution and cell cycle related protein expressions (cyclin D, cyclin A and cdc2) by hsp25 overexpression were also recovered by ERK2 cDNA transfection. Increase in Bcl-2 protein by hsp25 gene transfection was also reduced by subsequent ERK2 cDNA-transfection. Taken together, these results suggest that downregulation of ERK2 is essential for the inhibition of radiation-induced cell death in HSP25 overexpressed cells.
Files in This Item:
T200208956.pdf Download
DOI
10.1038/sj/cdd/4400979
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Lee, Yun Sil(이윤실)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/144317
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