TY  - EJOU
AU  - Wittnebel, S. 
AU  - Jalil, A. 
AU  - Thiery, J. 
AU  - DaRocha, S. 
AU  - Viey, E. 
AU  - Escudier, B. 
AU  - Chouaib, S. 
AU  - Caignard, A. 

TI  - The sensitivity of renal cell carcinoma cells to interferon alpha correlates with p53-induction and involves Bax
T2  - European Cytokine Network

PY  - 2005
VL  - 16
IS  - 2
SN  - 1952-4005

AB  - Interferon alpha (IFN-α) 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-α has been proposed in other tumor models (hepatoblastoma). We therefore studied
the expression of p53 during IFN-α treatment using two freshly established RCC cell lines RCC5 and RCC7.
While IFN-α treatment significantly enhanced the expression of p53 in RCC7, no changes were observed in RCC5.
Cell viability under IFN-α remained unchanged in both cell lines. Following γ-irradiation, a p53-activating
stimulus, an enhanced cell death was observed in IFN-α-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-α and γ-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-α.
KW  - interferon a
KW  -  renal cell carcinoma
KW  -  p53
KW  -  Bax

DO  -