STANDARD_NAME PANGAS_TUMOR_SUPPRESSION_BY_SMAD1_AND_SMAD5_UP SYSTEMATIC_NAME M2185 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/PANGAS_TUMOR_SUPPRESSION_BY_SMAD1_AND_SMAD5_UP NAMESPACE MOUSE_SEQ_ACCESSION DESCRIPTION_BRIEF Genes up-regulated in ovarian tumors from mouse models for the BMP SMAD signaling (gonad specific double knockout of SMAD1 and SMAD5 [GeneID=4086, 4090]). DESCRIPTION_FULL The transforming growth factor beta (TGFbeta) family has critical roles in the regulation of fertility. In addition, the pathogenesis of some human cancers is attributed to misregulation of TGFbeta function and SMAD2 or SMAD4 mutations. There are limited mouse models for the BMP signaling SMADs (BR-SMADs) 1, 5, and 8 because of embryonic lethality and suspected genetic redundancy. Using tissue-specific ablation in mice, we deleted the BR-SMADs from somatic cells of ovaries and testes. Single conditional knockouts for Smad1 or Smad5 or mice homozygous null for Smad8 are viable and fertile. Female double Smad1 Smad5 and triple Smad1 Smad5 Smad8 conditional knockout mice become infertile and develop metastatic granulosa cell tumors. Male double Smad1 Smad5 conditional knockout mice are fertile but demonstrate metastatic testicular tumor development. Microarray analysis indicated significant alterations in expression of genes related to the TGFbeta pathway, as well as genes involved in infertility and extracellular matrix production. These data strongly implicate the BR-SMADs as part of a critical developmental pathway in ovaries and testis that, when disrupted, leads to malignant transformation. PMID 17967875 GEOID GSE8156 AUTHORS Pangas SA,Li X,Umans L,Zwijsen A,Huylebroeck D,Gutierrez C,Wang D,Martin JF,Jamin SP,Behringer RR,Robertson EJ,Matzuk MM CONTRIBUTOR Arthur Liberzon CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 2S FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS AB000828,AF220015,AF378760,AF440737,AI327038,AI451865,AI481797,AI593746,AI647775,AJ311773,AK007400,AK009372,AK010212,AK010452,AK011827,AK013788,AK014221,AK018172,AK018466,AV014063,AV016515,AV025559,AV027151,AV066667,AV074236,AV231210,AV232123,AV245241,AV278332,AV293368,AV297525,AV308222,AV339861,AV360881,AV366661,AW049660,AW208509,AW208566,AW536432,AY059394,BB022070,BB041811,BB096079,BB113173,BB114398,BB125806,BB126796,BB151715,BB168690,BB207647,BB218107,BB234337,BB291880,BB328287,BB332932,BB336256,BB356861,BB359521,BB379724,BB386177,BB431371,BB457124,BB458758,BB468566,BB476944,BB519218,BB530087,BB533460,BB667096,BB795614,BB815011,BB827685,BC001999,BC004753,BC005429,BC009660,BC010191,BC011462,BC016109,BC016230,BC016562,BC020001,BC026867,BC027199,BE849316,BE915338,BE947079,BF021001,BF147716,BF166604,BF581690,BF585144,BG067463,BG069873,BI147002,BI217574,BI409701,BI452727,BI733057,BM117900,BM118190,BM120495,BM207712,BM228780,BM247104,BM936013,BQ175501,C76969,L20048,M58566,M74124,NM_007557,NM_007572,NM_008137,NM_008330,NM_008377,NM_008879,NM_008880,NM_009079,NM_009256,NM_009692,NM_009781,NM_009964,NM_010296,NM_010362,NM_011125,NM_011254,NM_011641,NM_011812,NM_016900,NM_017464,NM_020008,NM_021278,NM_021531,NM_022024,NM_025273,NM_025508,NM_025974,NM_026517,NM_027828,NM_030889,NM_033327,NM_080638,NM_133214,NM_133918,NM_134131,U16321,U63408,U66888,X14480,X58380,X63440 GENE_SYMBOLS TYRO3,TRIM5,PLXDC1,CST12P,CDK14,DTD1,IFI16,ANGPTL1,CHCHD10,ART3,LBH,RFTN1,PKIA,ARHGEF25,UNC13D,CAMK2N2,BMPER,PRUNE2,RBMS3,SMAD5,CRYAB,GSN,LASP1,SMIM22,S100A16,STOX2,,,GXYLT2,MCF2L,KMT2C,,NHSL2,LITAF,TMEM204,NFIX,SEPTIN4,LYZ,HS6ST2,CADM4,L3MBTL3,TGM2,,TRPT1,COL12A1,TMEM178B,,ETS1,EFS,,LAPTM5,C16orf54,HDGFL3,,LRRC4,,NFATC1,VEGFD,CCL27,ENOX1,NAV1,,SMTNL2,,EYA4,CPD,OTUD1,TGFBI,CELF2,ZHX3,SNX24,RGMA,EMP3,L3HYPDH,MATN2,CAVIN3,PTPN1,FGD1,,BAG2,TCIM,ALDH1B1,TMCC3,LRRK1,TAOK3,IARS1,,NUAK1,MMP2,NIBAN2,ZG16,RGS5,APBB2,,TTC39A,SARDH,EVA1B,FSTL1,,DOC2B,CACNA1C,SEPTIN11,PAICS,SPIN1,KLHL6,SIPA1L1,CAMKMT,WIPF1,IL2RG,ZFP36L1,IFI16,BMP7,C1QA,GNA14,,LRIG1,LCP1,PLSCR1,RPL22,SERPINB9,APOA1,CACNA1C,CRYAB,GLI1,GSTO1,PLTP,RBP1,TP63,FBLN5,CAV2,NEDD9,CLEC7A,TMSB4X,CARM1,GMFG,PCBD1,GMPR,RPL14,RPL22L1,FAM110C,SORCS2,ZNF423,MVP,SMCO4,EMILIN1,TNFAIP8,TCF4,IRAG1,ADGRE1,NID1,HMGA2,PTPN12 FOUNDER_NAMES