Inman, G. J. and Allday, M. J. (2000) Apoptosis induced by TGF- 1 in Burkitt's lymphoma cells is caspase 8 dependent but is death receptor independent. Journal of Immunology, 165(5), pp. 2500-2510. (doi: 10.4049/jimmunol.165.5.2500) (PMID:10946276)
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Abstract
TGF-β is a potent inducer of apoptosis in many Burkitt’s lymphoma (BL) cell lines. In this study, we characterize this apoptotic process in the EBV-negative BL41 cell line. Induction of apoptosis was detected as early as 8 h after TGF-β treatment, as assayed by TUNEL and poly(ADP-ribose) polymerase cleavage. FACS analysis demonstrates that this proceeds predominately from the G1, but also from the G2/M phases of the cell cycle. We observed no early detectable changes in the steady-state levels of Bcl-2 and several of its family members after TGF-β treatment. We detected cleavage of caspases 2, 3, 7, 8, and 9 into their active subunits. Consistent with the involvement of these enzymes in TGF-β-mediated apoptosis, the broad spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(Ome)-flouromethylketone (ZVAD-fmk) blocked TGF-β-induced apoptosis and revealed a G1 arrest in treated cells. Use of specific caspase inhibitors revealed that the induction of apoptosis is caspase 8 dependent, but caspase 3 independent. Activation of caspase 8 has been shown to be a critical event in death receptor-mediated apoptosis. However, TGF-β treatment of BL41 cells was found not to affect the cell surface expression of Fas, TNF-R1, DR3, DR4, or DR5, or the steady-state expression levels of Fas ligand, TNF-R1, DR3, DR4, and DR5. Furthermore, blocking experiments indicated that TGF-β-mediated apoptosis is not dependent on Fas ligand, TNF-α, tumor necrosis-like apoptosis-inducing ligand, or TNF-like weak inducer of apoptosis signaling. Therefore, it appears that TGF-β induces apoptosis in BL cell lines via caspase 8 in a death receptor-independent fashion.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by The Wellcome Trust Project Grants 047383 and 050096 to M.J.A. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Inman, Professor Gareth |
| Authors: | Inman, G. J., and Allday, M. J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Journal of Immunology |
| Journal Abbr.: | American Association of Immunologists |
| ISSN: | 0022-1767 |
| ISSN (Online): | 1550-6606 |
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