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 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)
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External links |
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Filtered by similarity ?
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Source species |
Homo sapiens |
Contributed by |
Arthur Liberzon (MSigDB Team) |
Source platform or identifier namespace |
HUMAN_SEQ_ACCESSION |
Dataset references |
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format: grp | gmt | xml | json | TSV metadata |
Compute overlaps ? |
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Compendia expression profiles ? |
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
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Advanced query |
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these 26 genes
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Gene families ? |
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26 genes by gene family
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Show members |
(show 31 source identifiers mapped to 26 genes)
Source Id |
NCBI (Entrez) Gene Id |
Gene Symbol |
Gene Description |
AB023177 |
221981 |
THSD7A |
thrombospondin type 1 domain containing ... |
AB049150 |
23089 |
PEG10 |
paternally expressed 10 [Source:HGNC Sym... |
AF131741 |
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AF486622 |
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AK022035 |
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AK027618 |
221806 |
VWDE |
von Willebrand factor D and EGF domains ... |
AK129833 |
7980 |
TFPI2 |
tissue factor pathway inhibitor 2 [Sourc... |
BC010607 |
3480 |
IGF1R |
insulin like growth factor 1 receptor [S... |
BC010934 |
26137 |
ZBTB20 |
zinc finger and BTB domain containing 20... |
BC034328 |
79191 |
IRX3 |
iroquois homeobox 3 [Source:HGNC Symbol;... |
NM_000104 |
1545 |
CYP1B1 |
cytochrome P450 family 1 subfamily B mem... |
NM_000165 |
2697 |
GJA1 |
gap junction protein alpha 1 [Source:HGN... |
NM_000474 |
7291 |
TWIST1 |
twist family bHLH transcription factor 1... |
NM_001792 |
1000 |
CDH2 |
cadherin 2 [Source:HGNC Symbol;Acc:HGNC:... |
NM_003070 |
6595 |
SMARCA2 |
SWI/SNF related, matrix associated, acti... |
NM_003937 |
8942 |
KYNU |
kynureninase [Source:HGNC Symbol;Acc:HGN... |
NM_004867 |
9452 |
ITM2A |
integral membrane protein 2A [Source:HGN... |
NM_005233 |
2042 |
EPHA3 |
EPH receptor A3 [Source:HGNC Symbol;Acc:... |
NM_006393 |
10529 |
NEBL |
nebulette [Source:HGNC Symbol;Acc:HGNC:1... |
NM_006528 |
7980 |
TFPI2 |
tissue factor pathway inhibitor 2 [Sourc... |
NM_012302 |
23266 |
ADGRL2 |
adhesion G protein-coupled receptor L2 [... |
NM_013390 |
23670 |
CEMIP2 |
cell migration inducing hyaluronidase 2 ... |
NM_016951 |
51192 |
CKLF |
chemokine like factor [Source:HGNC Symbo... |
NM_018003 |
55075 |
UACA |
uveal autoantigen with coiled-coil domai... |
NM_022073 |
112399 |
EGLN3 |
egl-9 family hypoxia inducible factor 3 ... |
NM_031418 |
63982 |
ANO3 |
anoctamin 3 [Source:HGNC Symbol;Acc:HGNC... |
NM_080629 |
1301 |
COL11A1 |
collagen type XI alpha 1 chain [Source:H... |
NM_145791 |
4257 |
MGST1 |
microsomal glutathione S-transferase 1 [... |
NM_173550 |
203238 |
CCDC171 |
coiled-coil domain containing 171 [Sourc... |
NM_181641 |
51192 |
CKLF |
chemokine like factor [Source:HGNC Symbo... |
U43328 |
1404 |
HAPLN1 |
hyaluronan and proteoglycan link protein... |
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Version history |
3.0: First introduced
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