Effect of bcl-2 on Fas antigen-mediated cell death.

Fas Ag is a cell surface protein that can mediate apoptosis and belongs to the TNF receptor family. The product of protooncogene bcl-2, a membrane-associated protein, has been shown to inhibit apoptosis in various hematopoietic cells including B cells and T cells. To examine the possible interaction of the Fas Ag and bcl-2, we coexpressed human Fas Ag and bcl-2 cDNA in murine IL-3-dependent FDC-P1 cell line and murine lymphoma WR19L. FDC-P1 transformants expressing bcl-2 showed a prolonged survival to IL-3 depletion. FDC-P1 transformants expressing the Fas Ag alone were killed by anti-Fas antibody in the presence of IL-3. Overexpression of bcl-2 in FDC-P1 resulted in a partial inhibition of Fas-induced cell death. WR19L transformants expressing bcl-2 were partially resistant to the cytolytic activities of the TNF-alpha and anti-Fas antibody treatment. These results suggest that the Fas Ag and TNF receptor may share the same signaling pathway, and that bcl-2 interferes with the apoptotic process mediated by the Fas Ag and TNF receptor.