ISSN:
1422-0067
Content:
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.
In:
International journal of molecular sciences, Basel : Molecular Diversity Preservation International, 2000-, Band 19, Heft 3 (2018), Seite 1-18, Artikel-ID: 767, 1422-0067
In:
volume:19
In:
year:2018
In:
number:3
In:
pages:1-18
In:
extent:18
In:
elocationid:767
Language:
English
DOI:
10.3390/ijms19030767
URN:
urn:nbn:de:hebis:30:3-458323