STANDARD_NAME	LANDIS_ERBB2_BREAST_PRENEOPLASTIC_UP
SYSTEMATIC_NAME	M15209
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/LANDIS_ERBB2_BREAST_PRENEOPLASTIC_UP
NAMESPACE	AFFY_MG_U74
DESCRIPTION_BRIEF	Up-regulated genes from top 82 genes out of the 324-gene signature identified in the pre-neoplastic tissue adjacent to 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 2: Increased in adjacent erbB2/neu samples
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	100522_s_at,102001_at,102198_at,102381_at,102896_at,103051_at,103064_at,103421_at,103721_at,104480_at,160249_at,160564_at,160695_i_at,160801_at,161227_r_at,162313_f_at,92927_at,93013_at,93568_i_at,96135_at,97165_r_at,97413_at,99584_at,99607_at
GENE_SYMBOLS	TCEAL9,RRM2,KCNN4,ACSL4,DOK1,,CHEK1,FRRS1,NPNT,DSG2,TPD52,LCN2,HOMER2,SLC66A2,,,ETV1,ID2,,ABRACL,,PLET1,CD82,SKP1
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