STANDARD_NAME	LANDIS_ERBB2_BREAST_TUMORS_65_DN
SYSTEMATIC_NAME	M13715
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/LANDIS_ERBB2_BREAST_TUMORS_65_DN
NAMESPACE	AFFY_MG_U74
DESCRIPTION_BRIEF	Down-regulated genes from the 65 most significantly changed (p<0.01) genes identified by two analytical methods 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,Montañez-Wiscovich ME,Danielpour D,Keri RA
CONTRIBUTOR	Leona Saunders
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 1: Decreased in tumors
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	100597_at,101110_at,101676_at,101867_at,102302_at,103568_at,104194_at,104313_at,104406_at,104494_at,104605_at,160373_i_at,160941_at,162044_f_at,162234_f_at,92742_at,93100_at,93353_at,93498_s_at,93568_i_at,93728_at,93983_at,93994_at,94516_f_at,94778_at,95016_at,95064_at,95485_at,95646_at,96206_at,96608_at,96742_at,96865_at,96900_at,96920_at,98312_at,98633_at,98984_f_at,99571_at,99579_at,99580_s_at,99622_at
GENE_SYMBOLS	GYG1,COL6A3,GPX3,GPAM,BCKDHB,SRPX,HEPH,PGM1,PTGES,SOWAHC,ADIPOR2,CAVIN2,PDE8A,,,CCL11,ACTA2,LUM,APLP2,,TSC22D1,DERL1,CHPT1,PENK,ALDH1A1,NRP1,ACAA2,HADH,CPT2,PHLDB1,PHYH,DPT,MARCKS,CHCHD10,HTRA1,RSPO1,TMEM43,GPD2,ACAA1,ATP1B3,UGT1A10,KLF4
FOUNDER_NAMES