STANDARD_NAME	BALDWIN_PRKCI_TARGETS_UP
SYSTEMATIC_NAME	M16912
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BALDWIN_PRKCI_TARGETS_UP
NAMESPACE	AFFY_HG_U133
DESCRIPTION_BRIEF	Genes up-regulated in U87MG cells (glioblastoma multiforme) after knockdown of PRKCI [GeneID=5584] by RNAi.
DESCRIPTION_FULL	Glioblastoma multiforme is an aggressive form of brain cancer that responds poorly to chemotherapy and is generally incurable. The basis for the poor response of this cancer to chemotherapy is not well understood. The atypical protein kinases C (PKCiota and PKCzeta) have previously been implicated in leukaemia cell chemoresistance. To assess the role of atypical PKC in glioblastoma cell chemoresistance, RNA interference was used to deplete human glioblastoma cells of PKCiota. Transfection of cells with either of two different RNA duplexes specific for PKCiota caused a partial sensitisation to cell death induced by the chemotherapy agent cisplatin. To screen for possible mechanisms for PKCiota-mediated chemoresistance, microarray analysis of gene expression was performed on RNA from glioblastoma cells that were either untreated or depleted of PKCiota. This identified sets of genes that were regulated either positively or negatively by PKCiota. Within the set of genes that were negatively regulated by PKCiota, the function of the gene coding for GMFbeta, an enhancer of p38 mitogen-activated protein kinase (MAP kinase) signaling, was investigated further, as the p38 MAP kinase pathway has been previously identified as a key mediator of cisplatin cytotoxicity. The expression of both GMFbeta mRNA and protein increased upon PKCiota depletion, and this was accompanied by an increase in cisplatin-activated p38 MAP kinase signaling. Transient overexpression of GMFbeta increased cisplatin-activated p38 MAP kinase signaling and also sensitised cells to cisplatin cytotoxicity. The increase in cisplatin cytotoxicity seen with PKCiota depletion was blocked by the p38 MAP kinase inhibitor SKF86002. These data show that PKCiota can confer partial resistance to cisplatin in glioblastoma cells by suppressing GMFbeta-mediated enhancement of p38 MAP kinase signaling.
PMID	16331246
GEOID	
AUTHORS	Baldwin RM,Garratt-Lalonde M,Parolin DA,Krzyzanowski PM,Andrade MA,Lorimer IA
CONTRIBUTOR	Jessica Robertson
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Fig 5B: Fold change > 1
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	201018_at,201308_s_at,201427_s_at,201601_x_at,201764_at,202048_s_at,202479_s_at,202543_s_at,203123_s_at,203124_s_at,203588_s_at,203834_s_at,204501_at,204639_at,205387_s_at,205410_s_at,205568_at,205792_at,205943_at,206087_x_at,206825_at,206874_s_at,207824_s_at,208737_at,208770_s_at,208877_at,209109_s_at,209884_s_at,211332_x_at,211976_at,212040_at,212043_at,212099_at,212158_at,212299_at,212444_at,212535_at,213156_at,213158_at,213306_at,213358_at,214808_at,216705_s_at,218519_at,218881_s_at,219321_at
GENE_SYMBOLS	EIF1AX,SEPTIN11,SELENOP,IFITM1,TMEM106C,CBX6,TRIB2,GMFB,SLC11A2,SLC11A2,TFDP2,TGOLN2,CCN3,ADA,CGB3,ATP2B4,AQP9,CCN5,TDO2,HFE,OXTR,SLK,MAZ,ATP6V1G1,EIF4EBP2,PAK2,TSPAN6,SLC4A7,HFE,NUDT3,TGOLN2,TGOLN2,RHOB,SDC2,NEK9,GPRC5A,MEF2A,ZBTB20,ZBTB20,MPDZ,MTCL1,TRIM56,ADA,SLC35A5,FOSL2,PALS1
FOUNDER_NAMES