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<MSIGDB BUILD_DATE="Jan 29, 2026" VERSION="2026.1.Hs" NAME="export">
    <GENESET STANDARD_NAME="LANDIS_ERBB2_BREAST_PRENEOPLASTIC_UP" SYSTEMATIC_NAME="M15209" HISTORICAL_NAMES="" PMID="15897883" AUTHORS="Landis MD,Seachrist DD,Montañez-Wiscovich ME,Danielpour D,Keri RA" GEOID="GSE2528" EXACT_SOURCE="Table 2: Increased in adjacent erbB2/neu samples" GENESET_LISTING_URL="" EXTERNAL_DETAILS_URL="" CHIP="AFFY_MG_U74" CONTRIBUTOR="Leona Saunders" CONTRIBUTOR_ORG="MSigDB Team" 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." TAGS="" 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" MEMBERS_SYMBOLIZED="ABRACL,ACSL4,CD82,CHEK1,DOK1,DSG2,ETV1,FRRS1,HOMER2,ID2,KCNN4,LCN2,NPNT,PLET1,RRM2,SKP1,SLC66A2,TCEAL9,TPD52" MEMBERS_EZID="1111,1796,1829,2115,2182,255743,3398,349633,3732,3783,391059,3934,51186,58527,6241,6500,7163,80148,9455" MEMBERS_MAPPING="100522_s_at,TCEAL9,51186|102001_at,RRM2,6241|102198_at,KCNN4,3783|102381_at,ACSL4,2182|102896_at,DOK1,1796|103051_at,null,null|103064_at,CHEK1,1111|103421_at,FRRS1,391059|103721_at,NPNT,255743|104480_at,DSG2,1829|160249_at,TPD52,7163|160564_at,LCN2,3934|160695_i_at,HOMER2,9455|160801_at,SLC66A2,80148|161227_r_at,null,null|162313_f_at,null,null|92927_at,ETV1,2115|93013_at,ID2,3398|93568_i_at,null,null|96135_at,ABRACL,58527|97165_r_at,null,null|97413_at,PLET1,349633|99584_at,CD82,3732|99607_at,SKP1,6500" FILTERED_BY_SIMILARITY="" FOUNDER_NAMES="" REFINEMENT_DATASETS="" VALIDATION_DATASETS="" CATEGORY_CODE="C2" ORGANISM="Mus musculus" SUB_CATEGORY_CODE="CGP"/>
</MSIGDB>
