APRIL, a new member of the tumor necrosis factor family, modulates death ligand-induced apoptosis

APRIL ((a) under bar (pr) under bar oliferation-(i) under bar nducing (l) u nder bar igand) is a newly identified member of the tumor necrosis factor ( TNF) family. Tumor growth-promoting as well as apoptosis-inducing effects o f APRIL have been described, Here, we report that five of 12 human malignan t glioma cell lines express APRIL. APRIL gene transfer experiments revealed that malignant glioma cells are refractory to growth-promoting activity of APRIL in vitro and in vivo. Interestingly, ectopic expression of APRIL con fers minor protection from apoptotic cell death induced by the death ligand s, CD95 ligand (CD95L) and tumor necrosis factor related apoptosis-inducing ligand (TRAIL)/Apo2 ligand (Apo2L), This antiapoptotic activity is specifi c for death ligand/receptor-mediated apoptosis since APRIL does not protect glioma cells from the cytotoxicity of the drugs, teniposide, vincristine, lomustine or cisplatin, Ectopic expression of APRIL is associated with the upregulation of X-linked inhibitor of apoptosis protein (XIAP), providing a possible explanation for the antiapoptotic activity observed here. In cont rast, APRIL does not regulate the expression levels of the antiapoptotic pr oteins FLICE-inhibitory protein (FLIP), Bcl-2 or Bcl-X-L. These findings su ggest that APRIL is involved in the regulation of death ligand-induced apop totic signaling in malignant glioma cells.