Effect of pH on radiation-induced p53 expression.
Int J Radiat Oncol Biol Phys
; 60(4): 1264-71, 2004 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-15519799
ABSTRACT
PURPOSE:
In most tumors, the intratumor environment is acidic. The purpose of this study was to elucidate the effect of acidic extracellular environment on the radiation-induced expression of p53 and related molecular signals. METHODS AND MATERIALS Cultured RKO.C human colorectal cancer cells carrying wild-type p53 were used. Cells grown in pH 7.5 medium or pH 6.6 medium were irradiated with gamma-rays, and the expression of p53 and p53 mRNA, as well as the degradation rate of the molecules, was determined. The transcriptional activity for p53 was investigated using cells transfected with a p53 reporter construct. The expression of Mdm2 and the phosphorylation of p53, essential factors for p53 degradation, were also investigated.RESULTS:
The pH 6.6 environment prolonged the radiation-induced expression of p53 and p53 mRNA. The radiation-induced increase in transcriptional activity of p53 lasted longer in pH 6.6 medium than in pH 7.5 medium. The degradation of p53 was delayed at pH 6.6. The radiation-induced expression of Mdm2 was markedly suppressed, whereas the phosphorylation of p53 was markedly increased after irradiation in pH 6.6 medium.CONCLUSION:
Acidic environment significantly enhances the radiation-induced expression of p53, partly by increasing the formation of p53 and also partly by slowing down the degradation of p53 through inhibiting p53-Mdm2 complex formation. The potential implication of acidic intratumor microenvironment for the response of tumors to radiotherapy remains to be elucidated.
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Base de dados:
MEDLINE
Assunto principal:
Proteína Supressora de Tumor p53
/
Concentração de Íons de Hidrogênio
Limite:
Humans
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article