PMID- 16140959
OWN - NLM
STAT- MEDLINE
DCOM- 20051115
LR  - 20121115
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 65
IP  - 17
DP  - 2005 Sep 1
TI  - Tumor necrosis factor-related apoptosis-inducing ligand-mediated proliferation of 
      tumor cells with receptor-proximal apoptosis defects.
PG  - 7888-95
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) might represent a 
      future cytotoxic drug to treat cancer as it induces apoptosis in tumor cells 
      without toxicity in animal trials. We recently described that in contrast to 
      apoptosis, TRAIL mediates tumor cell survival and proliferation in certain tumor 
      cells. Here we studied the effect of TRAIL on 18 cell lines and 53 primary 
      leukemia cells and classified these tumor cells into four groups: TRAIL, anti-DR4 
      or anti-DR5 induced apoptosis in group A cells, whereas they had no effect on 
      group 0 cells and mediated proliferation in group P cells. To our surprise, TRAIL 
      induced simultaneous apoptosis and proliferation in group AP cells. More than 20% 
      of all cells tested belonged to group P and showed TRAIL-mediated proliferation 
      even in the presence of certain cytotoxic drugs but not inhibitors of nuclear 
      factor-kappaB. Transfection with B-cell leukemia/lymphoma protein 2 transformed 
      group A cells into group 0 cells, whereas transfection with Fas-associated 
      polypeptide with death domain (FADD)-like interleukin-1-converting 
      enzyme-inhibitory protein (FLIP) transformed them into group AP cells. Loss of 
      caspase-8 or transfection of dominant-negative FADD transformed group A cells 
      into group P cells. Taken together, our data suggest that proliferation is a 
      frequent effect of TRAIL on tumor cells, which is related to receptor-proximal 
      apoptosis defects at the level of the death-inducing signaling complex and should 
      be prevented during antitumor therapy with TRAIL.
FAU - Baader, Eva
AU  - Baader E
AD  - Research Center Kubus , Dr. von Haunersches Kinderspital, Munich, Germany.
FAU - Toloczko, Agnieszka
AU  - Toloczko A
FAU - Fuchs, Uta
AU  - Fuchs U
FAU - Schmid, Irene
AU  - Schmid I
FAU - Beltinger, Christian
AU  - Beltinger C
FAU - Ehrhardt, Harald
AU  - Ehrhardt H
FAU - Debatin, Klaus-Michael
AU  - Debatin KM
FAU - Jeremias, Irmela
AU  - Jeremias I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (CASP8 and FADD-Like Apoptosis Regulating Protein)
RN  - 0 (CFLAR protein, human)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Cflar protein, mouse)
RN  - 0 (FADD protein, human)
RN  - 0 (Fadd protein, mouse)
RN  - 0 (Fas-Associated Death Domain Protein)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFSF10 protein, human)
RN  - 0 (Tnfsf10 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (Casp8 protein, mouse)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/antagonists & inhibitors/physiology
MH  - Amino Acid Chloromethyl Ketones/pharmacology
MH  - Animals
MH  - Apoptosis/*drug effects/physiology
MH  - Apoptosis Regulatory Proteins
MH  - CASP8 and FADD-Like Apoptosis Regulating Protein
MH  - Caspase 8
MH  - Caspase Inhibitors
MH  - Caspases/physiology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Fas-Associated Death Domain Protein
MH  - HT29 Cells/drug effects
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Leukemia/drug therapy/*pathology
MH  - Membrane Glycoproteins/*pharmacology
MH  - Mice
MH  - Neoplasms/drug therapy/*pathology
MH  - TNF-Related Apoptosis-Inducing Ligand
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2005/09/06 09:00
MHDA- 2005/11/16 09:00
CRDT- 2005/09/06 09:00
PHST- 2005/09/06 09:00 [pubmed]
PHST- 2005/11/16 09:00 [medline]
PHST- 2005/09/06 09:00 [entrez]
AID - 65/17/7888 [pii]
AID - 10.1158/0008-5472.CAN-04-4278 [doi]
PST - ppublish
SO  - Cancer Res. 2005 Sep 1;65(17):7888-95. doi: 10.1158/0008-5472.CAN-04-4278.