Wood, R. A., Barbour, M. J., Gould, G. W. , Cunningham, M. R. and Plevin, R. J. (2018) Conflicting evidence for the role of JNK as a target in breast cancer cell proliferation: comparisons between pharmacological inhibition and selective shRNA knockdown approaches. Pharmacology Research and Perspectives, 6(1), e00376. (doi: 10.1002/prp2.376)
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Abstract
As a target, the JNK pathway has been implicated in roles including cell death, proliferation, and inflammation in variety of contexts which span cardiovascular disease, neurodegenerative pathologies, and cancer. JNK1 and JNK2 have recently been demonstrated to function independently, highlighting a new parameter in the study of the JNK pathway. In order for JNK1 and JNK2-specific roles to be defined, better tools need to be employed. Previous studies have relied upon the broad spectrum JNK inhibitor, SP600125, to characterize the role of JNK signaling in a number of cell lines, including the breast cancer cell line MCF-7. In line with previous literature, our study has demonstrated that SP600125 treatment inhibited c-Jun and JNK phosphorylation and MCF-7 proliferation. However, in addition to targeting JNK1, JNK2, and JNK3, SP600125 has been previously demonstrated to suppress the activity of a number of other serine/threonine kinases, making SP600125 an inadequate tool for JNK isoform-specific roles to be determined. In this study, lentiviral shRNA was employed to selectively knockdown JNK1, JNK2, and JNK1/2 in MCF-7 cells. Using this approach, JNK phosphorylation was fully inhibited following stable knockdown of respective JNK isoforms. Interestingly, despite suppression of JNK phosphorylation, MCF-7 cell proliferation, cell cycle progression, or cell death remained unaffected. These findings raise the question of whether JNK phosphorylation really is pivotal in MCF-7 cell growth and death or if suppression of these events is a result of one of the many off-targets cited for SP600125.
Item Type: | Articles |
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Additional Information: | The study was supported by the University of Strathclyde. RW was funded by a University of Strathclyde funded PhD Studentship. MC is a University of Strathclyde Chancellor’s Fellow and AMS springboard recipient (SBF001\1009). |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Gould, Professor Gwyn |
Authors: | Wood, R. A., Barbour, M. J., Gould, G. W., Cunningham, M. R., and Plevin, R. J. |
College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
Journal Name: | Pharmacology Research and Perspectives |
Publisher: | Wiley |
ISSN: | 2052-1707 |
ISSN (Online): | 2052-1707 |
Published Online: | 20 December 2017 |
Copyright Holders: | Copyright © 2017 The Authors |
First Published: | First published in Pharmacology Research and Perspectives 691): e00376 |
Publisher Policy: | Reproduced under a Creative Commons License |
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