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<MSIGDB BUILD_DATE="Jan 29, 2026" VERSION="2026.1.Hs" NAME="export">
    <GENESET STANDARD_NAME="LANDIS_ERBB2_BREAST_TUMORS_65_UP" SYSTEMATIC_NAME="M6384" HISTORICAL_NAMES="" PMID="15897883" AUTHORS="Landis MD,Seachrist DD,Montañez-Wiscovich ME,Danielpour D,Keri RA" GEOID="GSE2528" EXACT_SOURCE="Table 1: Increased in tumors" GENESET_LISTING_URL="" EXTERNAL_DETAILS_URL="" CHIP="AFFY_MG_U74" CONTRIBUTOR="Leona Saunders" CONTRIBUTOR_ORG="MSigDB Team" DESCRIPTION_BRIEF="Up-regulated genes from the 65 most significantly changed (p&lt;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." TAGS="" 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" MEMBERS_SYMBOLIZED="ATP6V1A,BAG2,CD9,CMAS,CRADD,DAP,DSG2,DUSP6,FHDC1,GOLPH3,HAVCR1,IGF2R,ITPR2,LXN,MYDGF,NDST1,PDIA4,PERP,RAB18,SERP1,TPD52L1,WSB2" MEMBERS_EZID="1611,1829,1848,22931,26762,27230,3340,3482,3709,523,55884,55907,56005,56925,64065,64083,7164,85462,8738,928,9532,9601" MEMBERS_MAPPING="101441_i_at,ITPR2,3709|101446_at,TPD52L1,7164|102952_g_at,CRADD,8738|104207_at,FHDC1,85462|104480_at,DSG2,1829|160296_at,WSB2,55884|160688_at,GOLPH3,64083|160962_at,BAG2,9532|162302_f_at,null,null|93285_at,DUSP6,1848|93590_at,NDST1,3340|93842_at,DAP,1611|94319_at,RAB18,22931|95117_at,IGF2R,3482|95423_at,PDIA4,9601|95661_at,CD9,928|95708_at,SERP1,27230|95746_at,ATP6V1A,523|96065_at,LXN,56925|96318_at,MYDGF,56005|97335_at,HAVCR1,26762|97825_at,PERP,64065|98593_at,CMAS,55907" FILTERED_BY_SIMILARITY="" FOUNDER_NAMES="" REFINEMENT_DATASETS="" VALIDATION_DATASETS="" CATEGORY_CODE="C2" ORGANISM="Mus musculus" SUB_CATEGORY_CODE="CGP"/>
</MSIGDB>
