Recently, TRAIL has been demonstrated to selectively induce apoptosis in tr
ansformed cell lines, and subsequently four receptors (TRAIL-R1-TRAIL-R4) h
ave been identified. The ability to transduce death signals is restricted t
o TRAIL-R1/TRAIL-R2. In contrast, TRAIL-R3/TRAIL-R4 are unable to activate
apoptotic pathways and have therefore been suggested to act as "decoys" pro
tecting normal tissues from cell death, However, the biological role of the
TRAIL system remains incompletely understood. We analyzed the expression o
f TRAIL and its receptors in a panel of human brain tumors (n = 34) and in
four glioma cell lines in comparison to normal brain tissue. Constant co-ex
pression of TRAIL and of receptors TRAIL-R1, TRAIL-R2, and TRAIL-R3 in diff
erent tumor entities as well as in normal brain indicates that additional m
echanisms might modulate the previously proposed "decoy" model. Furthermore
, in contrast to previous reports, we demonstrate TRAIL and TRAIL-R2 to be
present on a transcriptional level in normal brain tissue. Exceptional expr
ession of TRAIL-R4 transcripts does not suggest a significant regulatory ro
le of this receptor in the human brain and its tumors. (C) 1999 Academic Pr
ess.