The sensitivity of renal cell carcinoma cells to interferon alpha correlates with p53-induction and involves Bax.
Eur Cytokine Netw
; 16(2): 123-7, 2005 Jun.
Article
em En
| MEDLINE
| ID: mdl-15941683
ABSTRACT
Interferon alpha (IFN-alpha) is an approved treatment in metastatic renal cell carcinoma (RCC). The underlying mechanisms are far from being clear, but are presumed to be a combination of stimulation of cell-mediated cytotoxicity, direct antiproliferative activity and antiangiogenic effects. Recently, the role of p53 in the cellular response to IFN-alpha has been proposed in other tumor models (hepatoblastoma). We therefore studied the expression of p53 during IFN-alpha treatment using two freshly established RCC cell lines RCC5 and RCC7. While IFN-alpha treatment significantly enhanced the expression of p53 in RCC7, no changes were observed in RCC5. Cell viability under IFN-alpha remained unchanged in both cell lines. Following gamma-irradiation, a p53-activating stimulus, an enhanced cell death was observed in IFN-alpha-treated RCC7 but not in RCC5. We further demonstrate that there were no changes in Bcl-2- and Bax-expression, two target genes regulated by p53. However, intracellular staining revealed that cell death induced by IFN-alpha and gamma-irradiation was preceded by a shift of Bax to the mitochondria in RCC7. Our results suggest a role of p53 and its downstream target Bax, in the control of RCC sensitivity to IFN-alpha.
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Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Renais
/
Proteína Supressora de Tumor p53
/
Interferon-alfa
/
Neoplasias Renais
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article