Gene Set: LI_CISPLATIN_RESISTANCE_UP

Standard name LI_CISPLATIN_RESISTANCE_UP
Systematic name M4717
Brief description Genes consistently up-regulated in ACRP cells (ovarian cancer, resistant to cisplatin [PubChem=2767]) compared to the parental sensitive A2780 cells, regardless of cisplatin exposure.
Full description or abstract The molecular pathways activated in response to acute cisplatin exposure, as well as the mechanisms involved in the long-term development of cisplatin-resistant cancer cells remain unclear. Using whole genome oligonucleotide microarrays, we have examined the kinetics of gene expression changes in a cisplatin-sensitive cell line, A2780, and its cisplatin-resistant derivative, ACRP. Both sensitive and resistant cell lines exhibited a very similar response of p53-inducible genes as early as 16 h after treatment. This p53 response was further increased at the 24-h time point. These experiments identify p53 as the main pathway producing a large-scale transcriptional response after cisplatin treatment in these cells containing wild-type p53. Consistent with a role for the p53 response in cisplatin sensitivity, knockdown of the p53 protein with small interfering RNA led to a twofold decrease in cell survival in the resistant cells. In addition, our analysis also allowed the identification of several genes that are differentially expressed between sensitive and resistant cells. These genes include GJA1 (encoding connexin 43 (Cx43)) and TWIST1, which are highly upregulated in cisplatin-resistant cells. The importance of Cx43 in drug resistance was demonstrated through functional analyses, although paradoxically, inhibition of Cx43 function in high expressing cells led to an increase in drug resistance. The pathways important in cisplatin response, as well as the genes found differentially expressed between cisplatin-resistant and -sensitive cells, may represent targets for therapy aimed at reversing drug resistance.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17072341   Authors: Li J,Wood WH 3rd,Becker KG,Weeraratna AT,Morin PJ
Exact source Table 1
Related gene sets (show 1 additional gene sets from the source publication)

(show 102 gene sets from the same authors)
External links  
Filtered by similarity
Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform HUMAN_SEQ_ACCESSION
Dataset references  
Download gene set format: grp | text | gmt | gmx | xml
Compute overlaps (show collections to investigate for overlap with this gene set)
Compendia expression profiles GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 26 genes
Gene families Categorize these 26 genes by gene family
Show members (show 31 members mapped to 26 genes)
Version history 3.0: First introduced

See MSigDB license terms here. Please note that certain gene sets have special access terms.