STANDARD_NAME LANDIS_ERBB2_BREAST_TUMORS_324_UP SYSTEMATIC_NAME M366 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/LANDIS_ERBB2_BREAST_TUMORS_324_UP NAMESPACE AFFY_MG_U74 DESCRIPTION_BRIEF Up-regulated genes from the 324 genes identified by two analytical methods as changed in the mammary tumors induced by transgenic expression of ERBB2 [GeneID=2064]. DESCRIPTION_FULL Upregulation of HER2/ErbB2/Neu occurs in 15-30% of human breast cancers and correlates with poor prognosis. Identification of ErbB2/Neu transcriptional targets should facilitate development of novel therapeutic approaches. Development of breast cancer is a multistep process; thus, to identify the transcriptomes associated with different stages of progression of tumorigenesis, we compared expression profiles of mammary tumors and preneoplastic mammary tissue from MMTV-Neu transgenic mice to expression profiles of wild-type mammary glands using Affymetrix microarrays. We identified 324 candidate genes that were unique to ErbB2/Neu-induced tumors relative to normal mammary gland tissue from wild-type controls. Expression of a subset of these genes (82) was also changed in the preneoplastic mammary glands compared to wild-type controls, indicating that they may play a pivotal role during early events of ErbB2/Neu-initiated mammary tumorigenesis. Further analysis of the microarray data revealed that expression of several known transforming growth factor (TGF)-beta target genes was altered, suggesting that the TGF-beta signaling cascade is downregulated in ErbB2/Neu-induced tumors. Western blot analysis for TGF-beta-Receptor-I/ALK5 and immunohistochemistry for TGF-beta-Receptor-I/ALK5 and phosphorylated/activated Smad2 confirmed that the Smad-dependent TGF-beta signaling cascade was inactive in these tumors. Although absent in most of the tumor, phosphorylated Smad2 was present in the periphery of tumors. Interestingly, presence of phosphorylated/activated Smad2 correlated with expression of Activin-Receptor-IB/ALK4, suggesting that although Smad-dependent TGF-beta signaling is absent in ErbB2/Neu-induced tumors, Activin signaling may be active at the leading edge of these tumors. Cumulatively, these data indicate that the TGF-beta pathway is intrinsically suppressed in ErbB2/Neu tumors via a mechanism involving loss of TGF-beta-Receptor-I/ALK5. PMID 15897883 GEOID GSE2528 AUTHORS Landis MD,Seachrist DD,MontaƱez-Wiscovich ME,Danielpour D,Keri RA CONTRIBUTOR Leona Saunders CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 2S: Fold change: TUvsWT > 1 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 100005_at,100024_at,100043_f_at,100084_at,100088_at,100128_at,100151_at,100472_at,100522_s_at,100948_at,101009_at,101019_at,101441_i_at,101446_at,101458_at,101996_at,102001_at,102043_at,102197_at,102198_at,102243_at,102283_at,102371_at,102381_at,102803_at,102896_at,102922_at,102936_at,102952_g_at,102988_at,103051_at,103059_at,103064_at,103321_at,103330_at,103345_at,103421_at,103423_at,103443_at,103494_at,103721_at,103794_i_at,103816_at,103892_r_at,104063_at,104170_at,104207_at,104434_at,104480_at,104577_at,160065_s_at,160109_at,160112_at,160149_at,160193_at,160202_at,160236_at,160249_at,160251_at,160270_at,160296_at,160343_at,160393_at,160546_at,160564_at,160622_at,160688_at,160695_i_at,160801_at,160806_at,160864_at,160872_f_at,160962_at,160973_at,160977_at,160979_at,161227_r_at,161696_f_at,162302_f_at,162313_f_at,162315_f_at,162482_at,92275_at,92325_at,92369_at,92440_at,92554_at,92564_at,92608_at,92927_at,93013_at,93281_at,93285_at,93293_at,93298_at,93590_at,93667_at,93674_at,93753_at,93842_at,93965_r_at,93975_at,94032_at,94231_at,94319_at,94384_at,94423_at,94453_at,94493_at,94532_at,94821_at,95022_at,95092_at,95117_at,95348_at,95423_at,95478_at,95518_at,95637_at,95654_at,95661_at,95708_at,95733_at,95745_g_at,95746_at,95952_at,96065_at,96090_g_at,96135_at,96318_at,96343_at,96518_at,96627_at,96682_at,96708_at,96771_at,97165_r_at,97206_at,97242_at,97335_at,97413_at,97689_at,97825_at,98071_f_at,98122_at,98143_at,98151_s_at,98477_s_at,98593_at,98596_s_at,98915_at,99011_at,99034_at,99109_at,99126_at,99452_at,99475_at,99500_at,99561_f_at,99582_at,99584_at,99607_at,99964_at GENE_SYMBOLS TRAF4,SHROOM3,PSAPL1,EZR,PPP1CB,CDK1,SERINC3,ENAH,TCEAL9,ANKH,KRT8,CTSC,ITPR2,TPD52L1,WEE1,PTPN2,RRM2,TUFT1,NUCB2,KCNN4,EHF,TIAM1,NR4A1,ACSL4,LIG3,DOK1,PITPNC1,B4GALT6,CRADD,INPPL1,,FXYD3,CHEK1,MOB1B,STRBP,SPTAN1,FRRS1,CYB561,CRYBG1,TSPAN8,NPNT,HAVCR1,F11R,ELL2,TOM1L1,MAPK8IP1,FHDC1,UNC119B,DSG2,MLH1,CSRP1,SOX4,CHMP2B,RAB10,ORMDL2,ATP6AP2,SLAIN1,TPD52,ZC3H15,LMAN1,WSB2,SRP19,ETNK1,ALDOC,LCN2,FLVCR2,GOLPH3,HOMER2,SLC66A2,STK39,RTKN,KNOP1,BAG2,CIP2A,ARHGEF5,CTBP2,,,,,,,TFAP2C,PTK7,TGFA,IRF6,CTBP2,LRRFIP1,CSRP1,ETV1,ID2,RCN2,DUSP6,CALM2,PAPSS1,NDST1,FBXW7,FGD1,LITAF,DAP,DDX6,ERRFI1,NAXE,CCND1,RAB18,IER3,SMAGP,MIEN1,CLDN3,ATP6V1E1,XBP1,AKAP12,PPP3CA,IGF2R,,PDIA4,SS18L2,RETREG1,FLNB,CLIC1,CD9,SERP1,SLC29A1,ATP6V1A,ATP6V1A,WNK2,LXN,C11orf54,ABRACL,MYDGF,ACTN4,WWC1,EBP,ST6GALNAC4,TMED3,ERBB3,,SPINT1,CYSTM1,HAVCR1,PLET1,F3,PERP,DCK,LMO4,FUT8,CTNND1,ANK3,CMAS,ST3GAL5,RNF149,GALNT3,IRX3,IER2,XIST,LSR,SOCS2,SLC12A2,CLDN7,EPCAM,CD82,SKP1,VDR FOUNDER_NAMES