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Radioresistant Burkitt’s lymphoma cells exhibit defective MAPK signalling
Author(s) -
MichaelRobinson Julie M.,
Spring Kevin J.,
Lavin Martin F.,
Watters Dianne J.
Publication year - 2001
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.1156
Subject(s) - ceramide , mapk/erk pathway , apoptosis , microbiology and biotechnology , radioresistance , kinase , p38 mitogen activated protein kinases , mitogen activated protein kinase , cell culture , biology , programmed cell death , cancer research , chemistry , biochemistry , genetics
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 al. [1997] Cancer Res 57:3600–3605). We show that p38 MAPK is activated transiently in both cells after ionising radiation. On the other 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 JNK 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. © 2001 Wiley‐Liss, Inc.