CD40 IS FUNCTIONALLY EXPRESSED ON HUMAN BREAST CARCINOMAS - VARIABLE INDUCIBILITY BY CYTOKINES AND ENHANCEMENT OF FAS-MEDIATED APOPTOSIS

The CD40 molecule, a member of the TNF receptor gene family, has been intensively studied with respect to regulation of B cell proliferation and survival. Although CD40 is also expressed on carcinoma cell lines , information concerning the biological function of CD40 on cells of e pithelial origin is limited. In this study we detected constitutive CD 40 on human breast carcinoma cell lines and an increase in CD40 expres sion following treatment with cytokines IL-1 alpha and IFN-gamma. CD40 ligation was also found to increase MHC II expression in cells pretre ated with IFN-gamma. In contrast to normal B cells, where CD40 signali ng provides a potent survival signal, we observed that CD40 ligation i n breast carcinoma cells results in growth inhibition and enhanced sus ceptibility to Fas-mediated apoptosis. Enhanced apoptosis appears to b e attributable, at least in part, to an up-regulation of Fas expressio n caused by CD40 ligation. These results suggest a potentially importa nt role for CD40 in breast tumor biology.