STANDARD_NAME	XU_HGF_TARGETS_INDUCED_BY_AKT1_48HR_UP
SYSTEMATIC_NAME	M17359
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/XU_HGF_TARGETS_INDUCED_BY_AKT1_48HR_UP
NAMESPACE	HUMAN_SEQ_ACCESSION
DESCRIPTION_BRIEF	Genes up-regulated in DU-145 cells (prostate cancer) in the absence but not in the presence of a dominant negative form of AKT1 [GeneID=207] upon exposure to HGF [GeneID=3082] for 48 h.
DESCRIPTION_FULL	The cytokine scatter factor (SF) (hepatocyte growth factor) transduces various biologic actions, including cell motility, invasion, angiogenesis and apoptosis inhibition. The latter is relevant to understanding the role of SF in promoting tumor cell survival in different contexts, for example, detachment from basement membrane, growth in metastatic sites and responses to chemo- and radiotherapy. Previously, we showed that SF protects cells against apoptosis owing to DNA damage, by a mechanism involving phosphoinositol-3-kinase/c-Akt signaling. Here, we used DNA microarray assays to identify c-Akt-regulated genes that might contribute to cell protection. DU-145 human prostate cancer cells were transfected+/-a dominant-negative mutant Akt, treated+/-SF and analysed for gene expression using Affymetrix arrays. These studies identified SF-regulated genes for which induction was c-Akt-dependent vs -independent. Selected microarray findings were confirmed by semiquantitative and quantitative reverse transcription-polymerase chain reaction. We tested the contribution of four SF-inducible/c-Akt-dependent genes (AMPD3, EPHB2, MX1 and WNT4) to protection against adriamycin (a DNA topoisomerase IIalpha inhibitor) using RNA interference. Knockdown of each gene except EPHB2 caused a small but significant reduction in the SF cell protection. The lack of effect of EPHB2 knockdown may be due to the fact that DU-145 cells contain a single-mutant EPHB2 allele. A combination of three small interfering RNAs blocked most of the protection by SF in both DU-145 and T47D cells. These findings identify novel c-Akt-regulated genes, some of which contribute to SF-mediated cytoprotection.
PMID	17099727
GEOID	
AUTHORS	Xu J,Gao M,Fan S,Meng Q,Goldberg ID,Abounader R,Ressom H,Laterra JJ,Rosen EM
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 4S
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	AF152509,D31661,M98478,NM_000428,NM_000480,NM_002425,NM_004472,NM_004848,NM_005242,NM_006058,NM_025106,NM_030761,U08839,U65932
GENE_SYMBOLS	,EPHB2,TGM2,LTBP2,AMPD3,MMP10,FOXD1,THEMIS2,F2RL1,TNIP1,SPSB1,WNT4,PLAUR,ECM1
FOUNDER_NAMES