STANDARD_NAME	STREICHER_LSM1_TARGETS_DN
SYSTEMATIC_NAME	M8637
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/STREICHER_LSM1_TARGETS_DN
NAMESPACE	HUMAN_GENE_SYMBOL
DESCRIPTION_BRIEF	Genes down-regulated in MCF10A cells (breast cancer) by expression of LSM1 [GeneID=27257] off a letiviral vector.
DESCRIPTION_FULL	Amplification of the 8p11-12 region occurs in 15-20% of breast cancers, but the driving oncogene at this locus has yet to be definitively identified. We mapped the 8p11-12 amplicon in breast cancer cell lines and primary human breast cancers and identified the candidate oncogene human Sm-like protein (hLsm1, LSM1) based on increases in copy number and expression level relative to human mammary epithelial cells. To examine the oncogenic role of LSM1, we overexpressed this gene in MCF10A mammary epithelial cells and inhibited its production in the SUM44 breast cancer cell line, which has a natural amplification and overexpression of LSM1. Our data confirmed that LSM1 is an oncogene from the 8p11-12 amplicon by showing that hLsm1 overexpression induced growth factor-independent proliferation and soft agar colony formation in MCF10A cells, and hLsm1 inhibition in SUM44 cells dramatically reduced soft agar growth. Little is known about hLsm1 function other than its involvement in mRNA degradation; therefore, we used expression microarray analysis to investigate how hLsm1 affects cell transformation in MCF10A and SUM44 cells. We identified numerous genes altered following hLsm1 overexpression common to SUM44 breast cancer cells that play important roles in cell cycle regulation, cell proliferation and other cancer-promoting processes. Future work will continue to characterize these important changes to achieve a more complete understanding of the mechanism of hLsm1's effect on cancer progression.
PMID	17001308
GEOID	
AUTHORS	Streicher KL,Yang ZQ,Draghici S,Ethier SP
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Fig 8B, 9
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	DUSP7,E2F7,ETS1,FGF2,FOXC2,FST,FZD8,ID1,IL15RA,IL1R2,IL1RAP,IL6,ITGB6,RBL1,SFRP1,TGFB1,TNFRSF10A,TNFRSF10B,WNT5,ZNF232
GENE_SYMBOLS	DUSP7,E2F7,ETS1,FGF2,FOXC2,FST,FZD8,ID1,IL15RA,IL1R2,IL1RAP,IL6,ITGB6,RBL1,SFRP1,TGFB1,TNFRSF10A,TNFRSF10B,,ZNF232
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