Expression of TRAIL and its receptors in human brain tumors.
Recently, TRAIL has been demonstrated to selectively induce apoptosis in transformed cell lines, and subsequently four receptors (TRAIL-R1-TRAIL-R4) have been identified. The ability to transduce death signals is restricted to 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" protecting normal tissues from cell death. However, the biological role of the TRAIL system remains incompletely understood. We analyzed the expression of 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-expression of TRAIL and of receptors TRAIL-R1, TRAIL-R2, and TRAIL-R3 in different tumor entities as well as in normal brain indicates that additional mechanisms 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 expression of TRAIL-R4 transcripts does not suggest a significant regulatory role of this receptor in the human brain and its tumors.
Frank
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S
Department of Surgical Research, Technical University of Dresden, Dresden, Germany. stfrank@helix.nih.gov
Köhler
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U
Schackert
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Schackert
H K
HK
D017398:Alternative Splicing / Q000235:genetics; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism*; D002460:Cell Line; D003110:Colonic Neoplasms / Q000378:metabolism; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007438:Introns / Q000235:genetics; D007962:Leukocytes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics*; D008954:Models, Biological; D009457:Neuroglia / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D053221:TNF-Related Apoptosis-Inducing Ligand; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D051017:Apoptosis Regulatory Proteins; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C108661:TNFRSF10C protein, human; C505653:TNFSF10 protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha