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 epithelial origin is limited. In this study we detected constitutive CD40 on human breast carcinoma cell lines and an increase in CD40 expression following treatment with cytokines IL-1alpha and IFN-gamma. CD40 ligation was also found to increase MHC II expression in cells pretreated with IFN-gamma. In contrast to normal B cells, where CD40 signaling provides a potent survival signal, we observed that CD40 ligation in breast carcinoma cells results in growth inhibition and enhanced susceptibility to Fas-mediated apoptosis. Enhanced apoptosis appears to be attributable, at least in part, to an up-regulation of Fas expression caused by CD40 ligation. These results suggest a potentially important role for CD40 in breast tumor biology.
Wingett
D G
DG
Department of Veterans Affairs Medical Center, Boise, Idaho 83702, USA.
Vestal
R E
RE
Forcier
K
K
Hadjokas
N
N
Nielson
C P
CP
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology*; D019013:CD40 Antigens / Q000096:biosynthesis* / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism*
D000970:Antineoplastic Agents; D019013:CD40 Antigens; D007375:Interleukin-1; D019014:fas Receptor; D007371:Interferon-gamma