title: The sensitivity of renal cell carcinoma cells to interferon alpha correlates with p53-induction and involves Bax.
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.
authors.affiliation: INSERM Unité 487, Cytokines et immunologie des tumeurs humaines, Institut Gustave-Roussy, 39 rue Camille-Desmoulins, 94805 Villejuif Cedex.
authors.forename: S
authors.initials: S
authors.lastname: Wittnebel
authors.forename: A
authors.initials: A
authors.lastname: Jalil
authors.forename: J
authors.initials: J
authors.lastname: Thiery
authors.forename: S
authors.initials: S
authors.lastname: DaRocha
authors.forename: E
authors.initials: E
authors.lastname: Viey
authors.forename: B
authors.initials: B
authors.lastname: Escudier
authors.forename: S
authors.initials: S
authors.lastname: Chouaib
authors.forename: A
authors.initials: A
authors.lastname: Caignard
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
chemical_list: D016898:Interferon-alpha; D016159:Tumor Suppressor Protein p53