Radioresistant Burkitt's lymphoma cells exhibit defective Mapk signalling

Michael-Robinson, J. M., Spring, K. J., Lavin, M. F. and Watters, D. J. (2001) Radioresistant Burkitt's lymphoma cells exhibit defective Mapk signalling. Drug Development Research, 52 4: 534-541. doi:10.1002/ddr.1156


Author Michael-Robinson, J. M.
Spring, K. J.
Lavin, M. F.
Watters, D. J.
Title Radioresistant Burkitt's lymphoma cells exhibit defective Mapk signalling
Journal name Drug Development Research   Check publisher's open access policy
ISSN 0272-4391
Publication date 2001
Sub-type Article (original research)
DOI 10.1002/ddr.1156
Volume 52
Issue 4
Start page 534
End page 541
Total pages 8
Editor Michael Williams
David J. Triggle
Place of publication USA
Publisher John Wiley & Sons, Inc
Collection year 2001
Language eng
Subject CX
270106 Cell Development (incl. Cell Division and Apoptosis)
730108 Cancer and related disorders
Abstract Using a pair of isogenic Burkitt's lymphoma cell lines, one of which is sensitive (BL30A) and the other resistant (BL30K) to apoptosis induced by ionising radiation and exogenous ceramide, we investigated mitogen-activated protein kinase (MAPK) signalling to determine which members of this kinase family are involved in the apoptotic process in these cells. We have previously shown that BL30A cells produce ceramide after irradiation and that this does not occur in BL30K cells (Michael et at. [1997] Cancer Res 57:3600-3605). We show that p38 MAPK is activated transiently in both cells after ionising radiation. On the of her hand, although JNK is rapidly activated in both cells, this activation is only transient in the resistant cells, whereas in the sensitive cells the activation is sustained. Addition of exogenous ceramide resulted in only a transient activation of INK in both cells. Interestingly, ERK activity was decreased in BL30A cells after ceramide treatment, whereas no such decrease occurred in the resistant cells. Treatment of BL30A cells with phorbol ester before irradiation, which blocks the increase in ceramide and apoptosis, also prevents the sustained increase in JNK activity. At the same time, ERK activity is increased. Our results suggest that p38 MAPK is not required for apoptosis signalling in response to ionising radiation in Burkitt's lymphoma cells and that sustained activation of JNK is necessary for apoptosis in these cells. These results also support the hypothesis that a balance between JNK and ERK activity determines cell fate after exposure to ceramide or ionising radiation. In addition, our results suggest different signalling pathways from exogenous ceramide and radiation, supporting the concept of different intracellular pools of active ceramide. Drug Dev. Res. 52:534-541, 2001. (C) 2001 Wiley-Liss, Inc.
Keyword Chemistry, Medicinal
Pharmacology & Pharmacy
Apoptosis
Ceramide
Jnk
P38
Ionising Radiation
Activated Protein-kinase
Radiation-induced Apoptosis
Stress-induced Apoptosis
Ionizing-radiation
Regulated Kinase
Signaling Pathway
Tyrosine Kinase
Resistance
Q-Index Code CX

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Tue, 14 Aug 2007, 15:48:12 EST