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Key Players of Cisplatin Resistance: Towards a Systems Pharmacology Approach.


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.

SUBMITTER: Sarin N 

PROVIDER: S-EPMC5877628 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Key Players of Cisplatin Resistance: Towards a Systems Pharmacology Approach.

Sarin Navin N   Engel Florian F   Rothweiler Florian F   Cinatl Jindrich J   Michaelis Martin M   Frötschl Roland R   Fröhlich Holger H   Kalayda Ganna V GV  

International journal of molecular sciences 20180307 3


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 A549<sup>r</sup>CDDP<sup>2000</sup> was screened with a whole genome  ...[more]

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