Downregulation of ERK2 is essential for the inhibition of radiation-induced cell death in HSP25 overexpressed L929 cells.
Cell Death Differ
; 9(4): 448-56, 2002 Apr.
Article
em En
| MEDLINE
| ID: mdl-11965498
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação para Baixo
/
Apoptose
/
Proteína Quinase 1 Ativada por Mitógeno
/
Proteínas de Choque Térmico
/
Proteínas de Neoplasias
Limite:
Animals
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article