| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Section of Virology and Cell Biology and the Ludwig Institute for Cancer Research, Imperial College of Science, Technology and Medicine, St. Mary’s Campus, London, United Kingdom
TGF-ß 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-ß 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-ß 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-ß-mediated apoptosis, the broad spectrum caspase inhibitor
benzyloxycarbonyl-Val-Ala-Asp(Ome)-flouromethylketone (ZVAD-fmk)
blocked TGF-ß-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-ß 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-ß-mediated apoptosis is not dependent
on Fas ligand, TNF-
, tumor necrosis-like apoptosis-inducing ligand,
or TNF-like weak inducer of apoptosis signaling. Therefore, it appears
that TGF-ß induces apoptosis in BL cell lines via caspase 8 in a
death receptor-independent fashion.
This article has been cited by other articles:
|
|
 |
|
  Y.-G. Chen, Z. Wang, J. Ma, L. Zhang, and Z. Lu Endofin, a FYVE Domain Protein, Interacts with Smad4 and Facilitates Transforming Growth Factor-beta Signaling J. Biol. Chem., March 30, 2007; 282(13): 9688 - 9695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. Bouker, T. C. Skaar, R. B. Riggins, D. S. Harburger, D. R. Fernandez, A. Zwart, A. Wang, and R. Clarke Interferon regulatory factor-1 (IRF-1) exhibits tumor suppressor activities in breast cancer associated with caspase activation and induction of apoptosis Carcinogenesis, September 1, 2005; 26(9): 1527 - 1535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Elliott and G. C. Blobe Role of Transforming Growth Factor Beta in Human Cancer J. Clin. Oncol., March 20, 2005; 23(9): 2078 - 2093. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-S. Choi, D.-S. Eom, B. S. Han, W. K. Kim, B. H. Han, E.-J. Choi, T. H. Oh, G. J. Markelonis, J. W. Cho, and Y. J. Oh Phosphorylation of p38 MAPK Induced by Oxidative Stress Is Linked to Activation of Both Caspase-8- and -9-mediated Apoptotic Pathways in Dopaminergic Neurons J. Biol. Chem., May 7, 2004; 279(19): 20451 - 20460. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fukuda and R. Longnecker Latent Membrane Protein 2A Inhibits Transforming Growth Factor-{beta}1-Induced Apoptosis through the Phosphatidylinositol 3-Kinase/Akt Pathway J. Virol., February 15, 2004; 78(4): 1697 - 1705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Dho and K.-S. Kwon The Ret Finger Protein Induces Apoptosis via Its RING Finger-B Box-Coiled-coil Motif J. Biol. Chem., August 22, 2003; 278(34): 31902 - 31908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. K. Binne, W. Amon, and P. J. Farrell Promoter Sequences Required for Reactivation of Epstein-Barr Virus from Latency J. Virol., September 11, 2002; 76(20): 10282 - 10289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Pifer, D. Robison, and P. E. Funk The Avian Chb6 Alloantigen Triggers Apoptosis in a Mammalian Cell Line J. Immunol., August 1, 2002; 169(3): 1372 - 1378. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Schrantz, M.-F. Bourgeade, S. Mouhamad, G. Leca, S. Sharma, and A. Vazquez p38-mediated Regulation of an Fas-associated Death Domain Protein-independent Pathway Leading to Caspase-8 Activation during TGFbeta -induced Apoptosis in Human Burkitt Lymphoma B Cells BL41 Mol. Biol. Cell, October 1, 2001; 12(10): 3139 - 3151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Besnault, N. Schrantz, M. T. Auffredou, G. Leca, M. F. Bourgeade, and A. Vazquez B Cell Receptor Cross-Linking Triggers a Caspase-8- Dependent Apoptotic Pathway That Is Independent of the Death Effector Domain of Fas-Associated Death Domain Protein J. Immunol., July 15, 2001; 167(2): 733 - 740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Inman, U. K. Binné, G. A. Parker, P. J. Farrell, and M. J. Allday Activators of the Epstein-Barr Virus Lytic Program Concomitantly Induce Apoptosis, but Lytic Gene Expression Protects from Cell Death J. Virol., March 1, 2001; 75(5): 2400 - 2410. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
