Sarin, Navin, Engel, Florian, Rothweiler, Florian, Cinatl, Jindrich, Michaelis, Martin, Frötschl, Roland, Fröhlich, Holger, Kalayda, Ganna V (2018) Key Players of Cisplatin Resistance: Towards a Systems Pharmacology Approach. International Journal of Molecular Sciences, 19 (3). pp. 767-785. ISSN 1422-0067. (doi:10.3390/ijms19030767) (KAR id:66690)
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Official URL: https://doi.org/10.3390/ijms19030767 |
Abstract
The major obstacle in the clinical use of the antitumor drug cisplatin is inherent and
acquired resistance. Typically, cisplatin resistance is not restricted to a single mechanism demanding
for a systems pharmacology approach to understand a whole cell’s reaction to the drug. In this
study, the cellular transcriptome of untreated and cisplatin-treated A549 non-small cell lung cancer
cells and their cisplatin-resistant sub-line A549rCDDP2000 was screened with a whole genome array
for relevant gene candidates. By combining statistical methods with available gene annotations
and without a previously defined hypothesis HRas, MAPK14 (p38), CCL2, DOK1 and PTK2B
were identified as genes possibly relevant for cisplatin resistance. These and related genes were
further validated on transcriptome (qRT-PCR) and proteome (Western blot) level to select candidates
contributing to resistance. HRas, p38, CCL2, DOK1, PTK2B and JNK3 were integrated into a model
of resistance-associated signalling alterations describing differential gene and protein expression
between cisplatin-sensitive and -resistant cells in reaction to cisplatin exposure.
Item Type: | Article |
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DOI/Identification number: | 10.3390/ijms19030767 |
Uncontrolled keywords: | cisplatin resistance; cellular signalling; HRas; p38; CCL2; DOK1; PTK2B; JNK3 |
Divisions: | Divisions > Division of Natural Sciences > Biosciences |
Depositing User: | Martin Michaelis |
Date Deposited: | 11 Apr 2018 14:16 UTC |
Last Modified: | 08 Dec 2022 21:35 UTC |
Resource URI: | https://kar.kent.ac.uk/id/eprint/66690 (The current URI for this page, for reference purposes) |
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