Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer.
Fas ligand (FasL) is produced by activated T cells and natural killer cells and it induces apoptosis (programmed cell death) in target cells through the death receptor Fas/Apol/CD95. One important role of FasL and Fas is to mediate immune-cytotoxic killing of cells that are potentially harmful to the organism, such as virus-infected or tumour cells. Here we report the discovery of a soluble decoy receptor, termed decoy receptor 3 (DcR3), that binds to FasL and inhibits FasL-induced apoptosis. The DcR3 gene was amplified in about half of 35 primary lung and colon tumours studied, and DcR3 messenger RNA was expressed in malignant tissue. Thus, certain tumours may escape FasL-dependent immune-cytotoxic attack by expressing a decoy receptor that blocks FasL.
Pitti
R M
RM
Department of Molecular Oncology, Molecular Biology, and Immunology, Genentech, Inc., South San Francisco, California 94080, USA.
Marsters
S A
SA
Lawrence
D A
DA
Roy
M
M
Kischkel
F C
FC
Dowd
P
P
Huang
A
A
Donahue
C J
CJ
Sherwood
S W
SW
Baldwin
D T
DT
Godowski
P J
PJ
Wood
W I
WI
Gurney
A L
AL
Hillan
K J
KJ
Cohen
R L
RL
Goddard
A D
AD
Botstein
D
D
Ashkenazi
A
A
D000328:Adult; D000595:Amino Acid Sequence; D017209:Apoptosis; D003110:Colonic Neoplasms / Q000235:genetics* / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D018076:DNA, Complementary; D020224:Expressed Sequence Tags; D053222:Fas Ligand Protein; D005784:Gene Amplification; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D008175:Lung Neoplasms / Q000235:genetics* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D019014:fas Receptor
D018076:DNA, Complementary; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C505911:TNFRSF6B protein, human; D019014:fas Receptor