Both TNF receptors are required for TNF-mediated induction of apoptosis in PC60 cells.

P Vandenabeele, W Declercq… - … (Baltimore, Md.: 1950 …, 1995 - journals.aai.org
P Vandenabeele, W Declercq, B Vanhaesebroeck, J Grooten, W Fiers
Journal of immunology (Baltimore, Md.: 1950), 1995journals.aai.org
A rat/mouse T cell hybridoma (PC60) was transfected either with human (h) TNF-R p55 (TNF-
R55), p75 (TNF-R75) or both cDNAs. hTNF-R55 expression was below 50 molecules/cell,
whereas the number of hTNF-R75 reached about 4000 molecules/cell. Only cells co-
expressing the two types of receptor showed TNF-dependent apoptosis, in contrast to cells
expressing similar levels of only one receptor type, indicating that both TNF-R55 and TNF-
R75 are required. Stable co-transfection of the bcl-2 proto-oncogene largely prevented this …
Abstract
A rat/mouse T cell hybridoma (PC60) was transfected either with human (h) TNF-R p55 (TNF-R55), p75 (TNF-R75) or both cDNAs. hTNF-R55 expression was below 50 molecules/cell, whereas the number of hTNF-R75 reached about 4000 molecules/cell. Only cells co-expressing the two types of receptor showed TNF-dependent apoptosis, in contrast to cells expressing similar levels of only one receptor type, indicating that both TNF-R55 and TNF-R75 are required. Stable co-transfection of the bcl-2 proto-oncogene largely prevented this TNF-mediated induction of apoptosis. We found that a high level of hTNF-R75 expression was essential for obtaining TNF-dependent apoptosis in PC60 cells in addition to a low number of hTNF-R55. Both receptors are signal transducing because simultaneous triggering of hTNF-R55 and hTNF-R75 by agonistic mAbs or by TNF-R-specific TNF muteins induced similar levels of apoptosis as wild-type hTNF. Apoptotic killing of only those lymphocytes expressing a high, induced level of TNF-R75, in addition to TNF-R55, may play a physiologically important role.
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