The sensitivity of renal cell carcinoma cells to interferon alpha correlates with p53-induction and involves Bax

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.