c-myc-induced apoptosis in polycystic kidney disease is independent of FasL/Fas interaction.
Apoptosis is a critical early cellular event in the development of polycystic kidney disease (PKD) in humans and mice. In the SBM transgenic model of PKD, both apoptosis and proliferation are c-myc driven and are independent of p53 and Bcl-2 pathways. On the basis of recent evidence implicating the FasL/Fas pathway in c-myc-induced apoptosis, we investigated the potential interaction of these pathways in vivo. We first evaluated the expression of FasL in renal tissues of SBM mice. This analysis showed that the level of FasL expression was elevated 3-4-fold in the SBM kidneys, indicating a potential autocrine suicidal mechanism. We next crossed the SBM mice with gld mice mutated in FasL. The progenies had comparable renal epithelial apoptotic and proliferation rates and a cystic phenotype in all SBM genotypes irrespective of the FasL genotype. Our study proves that c-myc-induced apoptosis can be independent of the FasL/Fas pathway in vivo and implicates the existence of a novel c-myc-driven apoptotic pathway.
Couillard
Martin
M
Institut de Recherches Cliniques de Montréal, Faculté de Médecine de l'Université de Montréal, Montréal, Québec, H2W 1R7 Canada.
Guillaume
Richard
R
Tanji
Nozomu
N
D'Agati
Vivette
V
Trudel
Marie
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D004847:Epithelial Cells / Q000473:pathology / Q000502:physiology; D053222:Fas Ligand Protein; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009154:Mutation; D007690:Polycystic Kidney Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D019014:fas Receptor / Q000502:physiology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D016271:Proto-Oncogene Proteins c-myc; D019014:fas Receptor