Abstract
The tumour suppressor gene p53 is mutated in approximately 50% of the human cancers. p53 is involved in genotoxic stress-induced cellular responses. The role of EGFR and ERK in DNA-damage-induced apoptosis is well known. We investigated the involvement of activation of ERK signalling as a consequence of non-functional p53, in sensitivity of cells to doxorubicin. We performed cell survival assays in cancer cell lines with varying p53 status: MCF-7 (wild-type p53, WTp53), MDA MB-468 (mutant p53, MUTp53), H1299 (absence of p53, NULLp53) and an isogenic cell line MCF-7As (WTp53 abrogated). Our results indicate that enhanced chemosensitivity of cells lacking wild-type p53 function is because of elevated levels of EGFR which activates ERK. Additionally, we noted that independent of p53 status, pERK contributes to doxorubicin-induced cell death.
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Acknowledgements
The authors thank Dr SC Mande, Director, NCCS, Pune, and Dr GC Mishra, former Director, NCCS, Pune, for their support and encouragement in carrying out this work. RK and SS thank the University Grants Commission (UGC), RRC and SC thank the Council for Scientific and Industrial Research (CSIR), AKA thanks the Indian Council of Medical Research (ICMR), India, for research fellowships. This work was supported in part by intramural funding from National Centre for Cell Science (NCCS), Department of Biotechnology (DBT), India. The funding agencies had no involvement in study design, data collection, interpretation and analysis, decision to publish or writing of the manuscript.
Work described in this paper is a part of thesis submitted by RK in 2010 to University of Pune, Pune.
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[Kumari R, Chouhan S, Singh S, Chhipa RR, Ajay AK and Bhat MK 2017 Constitutively activated ERK sensitizes cancer cells to doxorubicin: Involvement of p53-EGFR-ERK pathway. J. Biosci.]
Supplementary materials pertaining to this article are available on the Journal of Biosciences Website.
Ratna Kumari, Surbhi Chouhan and Snahlata Singh contributed equally to this work.
Supplementary materials pertaining to this article are available on the Journal of Biosciences Website.
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Kumari, R., Chouhan, S., Singh, S. et al. Constitutively activated ERK sensitizes cancer cells to doxorubicin: Involvement of p53-EGFR-ERK pathway. J Biosci 42, 31–41 (2017). https://doi.org/10.1007/s12038-017-9667-8
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DOI: https://doi.org/10.1007/s12038-017-9667-8