STANDARD_NAME	HUANG_FOXA2_TARGETS_DN
SYSTEMATIC_NAME	M16701
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/HUANG_FOXA2_TARGETS_DN
NAMESPACE	AFFY_HG_U133
DESCRIPTION_BRIEF	Genes down-regulated in H358 cells (lung cancer) by inducible expression of FOXA2 [GeneID=3170] in a Tet-off system.
DESCRIPTION_FULL	The forkhead transcription factor hepatocyte nuclear factor 3beta (HNF3beta) is essential in foregut development and the regulation of lung-specific genes. HNF3beta expression leads to growth arrest and apoptosis in lung cancer cells and HNF3beta is a candidate tumor suppressor in lung cancer. In a transcriptional profiling study using a conditional cell line system, we now identify 15-PGDH as one of the major genes induced by HNF3beta expression. 15-PGDH is a critical metabolic enzyme of proliferative prostaglandins, an antagonist to cyclooxygenase-2 and a tumor suppressor in colon cancer. We confirmed the regulation of 15-PGDH expression by HNF3beta in a number of systems and showed direct binding of HNF3beta to 15-PGDH promoter elements. Western blotting of lung cancer cell lines and immunohistochemical examination of human lung cancer tissues found loss of 15-PGDH expression in approximately 65% of lung cancers. Further studies using in vitro cell-based assays and in vivo xenograft tumorigenesis assays showed a lack of in vitro but significant in vivo tumor suppressor activity of 15-PGDH via an antiangiogenic mechanism analogous to its role in colon cancer. In summary, we identify 15-PGDH as a direct downstream effector of HNF3beta and show that 15-PGDH acts as a tumor suppressor in lung cancer.
PMID	18593902
GEOID	
AUTHORS	Huang G,Eisenberg R,Yan M,Monti S,Lawrence E,Fu P,Walbroehl J,Löwenberg E,Golub T,Merchan J,Tenen DG,Markowitz SD,Halmos B
CONTRIBUTOR	Leona Saunders
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 2S
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	200665_s_at,201042_at,201506_at,201645_at,201860_s_at,201998_at,202284_s_at,202998_s_at,203186_s_at,203256_at,203767_s_at,203769_s_at,203787_at,203851_at,203854_at,204490_s_at,204955_at,204990_s_at,205364_at,205387_s_at,206659_at,206785_s_at,206884_s_at,207069_s_at,207808_s_at,208978_at,209498_at,209729_at,209774_x_at,209875_s_at,209894_at,210845_s_at,211343_s_at,211924_s_at,212063_at,212136_at,213275_x_at,213428_s_at,213711_at,218424_s_at,219529_at,219956_at,31874_at
GENE_SYMBOLS	SPARC,TGM2,TGFBI,TNC,PLAT,ST6GAL1,CDKN1A,LOXL2,S100A4,CDH3,STS,STS,SSBP2,IGFBP6,CFI,CD44,SRPX,ITGB4,ACOX2,CGB3,,KLRC1,,SMAD6,PROS1,CRIP2,CEACAM1,GAS2L1,CXCL2,SPP1,LEPR,PLAUR,COL13A1,PLAUR,CD44,ATP2B4,CTSB,COL6A1,KRT81,STEAP3,CLIC3,GALNT6,GAS2L1
FOUNDER_NAMES