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<MSIGDB BUILD_DATE="Jan 29, 2026" VERSION="2026.1.Hs" NAME="export">
    <GENESET STANDARD_NAME="HUANG_FOXA2_TARGETS_DN" SYSTEMATIC_NAME="M16701" HISTORICAL_NAMES="" PMID="18593902" 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" GEOID="" EXACT_SOURCE="Table 2S" GENESET_LISTING_URL="" EXTERNAL_DETAILS_URL="" CHIP="AFFY_HG_U133" CONTRIBUTOR="Leona Saunders" CONTRIBUTOR_ORG="MSigDB Team" 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." TAGS="" 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" MEMBERS_SYMBOLIZED="ACOX2,ATP2B4,CD44,CDH3,CDKN1A,CEACAM1,CFI,CGB3,CLIC3,COL13A1,COL6A1,CRIP2,CTSB,CXCL2,GALNT6,GAS2L1,IGFBP6,ITGB4,KLRC1,KRT81,LEPR,LOXL2,PLAT,PLAUR,PROS1,S100A4,SMAD6,SPARC,SPP1,SRPX,SSBP2,ST6GAL1,STEAP3,STS,TGFBI,TGM2,TNC" MEMBERS_EZID="1001,1026,10634,1082,11226,1291,1305,1397,1508,23635,2920,3371,3426,3489,3691,3821,3887,3953,4017,4091,412,493,5327,5329,55240,5627,6275,634,6480,6678,6696,7045,7052,8309,8406,9022,960" MEMBERS_MAPPING="200665_s_at,SPARC,6678|201042_at,TGM2,7052|201506_at,TGFBI,7045|201645_at,TNC,3371|201860_s_at,PLAT,5327|201998_at,ST6GAL1,6480|202284_s_at,CDKN1A,1026|202998_s_at,LOXL2,4017|203186_s_at,S100A4,6275|203256_at,CDH3,1001|203767_s_at,STS,412|203769_s_at,STS,412|203787_at,SSBP2,23635|203851_at,IGFBP6,3489|203854_at,CFI,3426|204490_s_at,CD44,960|204955_at,SRPX,8406|204990_s_at,ITGB4,3691|205364_at,ACOX2,8309|205387_s_at,CGB3,1082|206659_at,null,null|206785_s_at,KLRC1,3821|206884_s_at,null,null|207069_s_at,SMAD6,4091|207808_s_at,PROS1,5627|208978_at,CRIP2,1397|209498_at,CEACAM1,634|209729_at,GAS2L1,10634|209774_x_at,CXCL2,2920|209875_s_at,SPP1,6696|209894_at,LEPR,3953|210845_s_at,PLAUR,5329|211343_s_at,COL13A1,1305|211924_s_at,PLAUR,5329|212063_at,CD44,960|212136_at,ATP2B4,493|213275_x_at,CTSB,1508|213428_s_at,COL6A1,1291|213711_at,KRT81,3887|218424_s_at,STEAP3,55240|219529_at,CLIC3,9022|219956_at,GALNT6,11226|31874_at,GAS2L1,10634" FILTERED_BY_SIMILARITY="" FOUNDER_NAMES="" REFINEMENT_DATASETS="" VALIDATION_DATASETS="" CATEGORY_CODE="C2" ORGANISM="Homo sapiens" SUB_CATEGORY_CODE="CGP"/>
</MSIGDB>
