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Cisplatin‐induced response of c‐jun N‐terminal kinase 1 and extracellular signal‐regulated protein kinases 1 and 2 in a series of cisplatin‐resistant ovarian carcinoma cell lines
Author(s) -
Cui Wei,
Yazlovitskaya Eugenia M.,
Mayo Matthew S.,
Pelling Jill C.,
Persons Diane L.
Publication year - 2000
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/1098-2744(200012)29:4<219::aid-mc1004>3.0.co;2-d
Subject(s) - cisplatin , kinase , mapk/erk pathway , biology , signal transduction , cell culture , extracellular , p38 mitogen activated protein kinases , cancer research , microbiology and biotechnology , chemotherapy , genetics
The cellular response to cisplatin involves activation of multiple signal transduction pathways, including the mitogen‐activated protein (MAP) kinase pathways. In this study, we compared the cisplatin‐induced activation of two MAP kinases, c‐jun N‐terminal kinase 1 (JNK1) and extracellular signal–regulated protein kinases 1 and 2 (ERK1/2), in the cisplatin‐sensitive ovarian carcinoma cell line A2780 and its derivative cisplatin‐resistant cell lines CP70 and C200. Dose‐dependent and time‐dependent activation of JNK1 and ERK1/2 occurred in each of the three cell lines in response to cisplatin treatment. The requirement of higher concentrations of cisplatin for induction of maximum activation of JNK1 and ERK1/2 was correlated with increased levels of cisplatin resistance. In addition, inhibition of cisplatin‐induced ERK activation, using the MAP/ERK kinase 1 synthetic inhibitor PD98059, resulted in enhanced sensitivity to cisplatin in all three cell lines. These results suggest that cisplatin‐induced ERK1/2 activity is not responsible for the acquired cisplatin resistance in CP70 and C200 cells but rather provides a general cytoprotective effect in both cisplatin‐sensitive and cisplatin‐resistant cell lines. In conclusion, different patterns of cisplatin‐induced JNK1 and ERK1/2 activation are observed in cell lines with different levels of cisplatin sensitivity, and inhibition of cisplatin‐induced ERK1/2 activation enhances sensitivity to cisplatin in both cisplatin‐sensitive and cisplatin‐resistant cell lines. Mol. Carcinog. 29:219–228, 2000. © 2000 Wiley‐Liss, Inc.