TY  - JOUR
A1  - Sarin, Navin
A1  - Engel, Florian
A1  - Rothweiler, Florian
A1  - Cinatl, Jindrich
A1  - Michaelis, Martin
A1  - Frötschl, Roland
A1  - Fröhlich, Holger
A1  - Kalayda, Ganna V.
T1  - Key players of cisplatin resistance : towards a systems pharmacology approach
T2  - International journal of molecular sciences
N2  - 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.
KW  - cisplatin resistance
KW  - cellular signalling
KW  - HRas
KW  - p38
KW  - CCL2
KW  - DOK1
KW  - PTK2B
KW  - JNK3
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45832
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-458323
SN  - 1422-0067
SN  - 1661-6596
N1  - This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
VL  - 19
IS  - 3, Art. 767
SP  - 1
EP  - 18
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -