STANDARD_NAME	LANDIS_ERBB2_BREAST_TUMORS_65_UP
SYSTEMATIC_NAME	M6384
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/LANDIS_ERBB2_BREAST_TUMORS_65_UP
NAMESPACE	AFFY_MG_U74
DESCRIPTION_BRIEF	Up-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: Increased in tumors
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	101441_i_at,101446_at,102952_g_at,104207_at,104480_at,160296_at,160688_at,160962_at,162302_f_at,93285_at,93590_at,93842_at,94319_at,95117_at,95423_at,95661_at,95708_at,95746_at,96065_at,96318_at,97335_at,97825_at,98593_at
GENE_SYMBOLS	ITPR2,TPD52L1,CRADD,FHDC1,DSG2,WSB2,GOLPH3,BAG2,,DUSP6,NDST1,DAP,RAB18,IGF2R,PDIA4,CD9,SERP1,ATP6V1A,LXN,MYDGF,HAVCR1,PERP,CMAS
FOUNDER_NAMES