Soluble Fas/APO-1 in tumor cells: a potential regulator of apoptosis?
Fas/APO-1, a member of the NGF/TNF receptor superfamily expressed on the cell-surface of normal and malignant cells, is known to induce cell death by apoptosis. In the present study, we have investigated Fas/APO-1 gene defects in a human osteosarcoma cell line resistant to the apoptosis-inducing effects of anti-Fas. cDNA cloning and sequencing revealed that these cells contained both 'authentic' and mutant Fas/APO-1 containing a 63 base pair in-frame deletion spanning the transmembrane domain, designated DFas/APO-1. Direct evidence for the existence of a soluble Fas/APO-1 protein was obtained by immunoprecipitation and Western blotting. Taken together with prior studies demonstrating a role for Fas/APO-1 and Fas ligand, respectively, in tumor target cell killing by cytotoxic T-lymphocytes, production of soluble Fas/APO-1 might have significant implications in malignant disease pathogenesis.
Owen-Schaub
L B
LB
Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Angelo
L S
LS
Radinsky
R
R
Ware
C F
CF
Gesner
T G
TG
Bartos
D P
DP
D000954:Antigens, Surface / Q000235:genetics* / Q000502:physiology; D017209:Apoptosis / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D001483:Base Sequence; D017353:Gene Deletion; D006801:Humans; D008969:Molecular Sequence Data; D012516:Osteosarcoma / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D016133:Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D014407:Tumor Cells, Cultured; D019014:fas Receptor
D000954:Antigens, Surface; D019014:fas Receptor