STANDARD_NAME	OLSSON_E2F3_TARGETS_UP
SYSTEMATIC_NAME	M18325
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/OLSSON_E2F3_TARGETS_UP
NAMESPACE	HUMAN_SEQ_ACCESSION
DESCRIPTION_BRIEF	Genes up-regulated in the 5637 cell line (bladder cancer) after knockdown of E2F3 [GeneID=1871] by RNAi.
DESCRIPTION_FULL	Amplification and overexpression of the E2F3 gene at 6p22 in human bladder cancer is associated with increased tumour stage, grade and proliferation index, and in prostate cancer E2F3 overexpression is linked to tumour aggressiveness. We first used small interfering RNA technology to confirm the potential importance of E2F3 overexpression in bladder cancer development. Knockdown of E2F3 expression in bladder cells containing the 6p22 amplicon strongly reduced the extent of bromodeoxyuridine (BrdU) incorporation and the rate of cellular proliferation. In contrast, knockdown of CDKAL1/FLJ20342, another proposed oncogene, from this amplicon had no effect. Expression cDNA microarray analysis on bladder cancer cells following E2F3 knockdown was then used to identify genes regulated by E2F3, leading to the identification of known E2F3 targets such as Cyclin A and CDC2 and novel targets including pituitary tumour transforming gene 1, Polo-like kinase 1 (PLK1) and Caveolin-2. For both bladder and prostate cancer, we have proposed that E2F3 protein overexpression may cooperate with removal of the E2F inhibitor retinoblastoma tumor suppressor protein (pRB) to drive cellular proliferation. In support of this model, we found that ectopic expression of E2F3a enhanced the BrdU incorporation, a marker of cellular proliferation rate, of prostate cancer DU145 cells, which lack pRB, but had no effect on the proliferation rate of PC3 prostate cancer cells that express wild-type pRB. BrdU incorporation in PC3 cells could, however, be increased by overexpressing E2F3a in cells depleted of pRB. When taken together, these observations indicate that E2F3 levels have a critical role in modifying cellular proliferation rate in human bladder and prostate cancer.
PMID	16909110
GEOID	GSE6131
AUTHORS	Olsson AY,Feber A,Edwards S,Te Poele R,Giddings I,Merson S,Cooper CS
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 1
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	AB018275,AF001893,AF350451,AK074108,AK091128,AK095239,AK095375,AK122936,AK160382,BC066552,BC066649,BE870210,BF035171,BG534134,BG739729,BQ939577,BX537368,BX538238,BX647186,BX648351,NM_001218,NM_004393,NM_004800,NM_006291,NM_016143,NM_019894,NM_173464,NM_198715,R34433,T88000,U67206
GENE_SYMBOLS	SMG6,,TENT5A,EEIG1,,AKR1C1,NECTIN1,SERPINH1,AKNA,LAMA4,C1orf198,,WFDC2,CCL20,S100A8,AKR1C3,ELF3,MALAT1,ECHDC2,ECE1,CA12,DAG1,TM9SF2,TNFAIP2,NSFL1C,TMPRSS4,L3MBTL4,PTGER3,,NSFL1C,CASP7
FOUNDER_NAMES