Gene Set: LANDIS_ERBB2_BREAST_TUMORS_65_DN

Standard name LANDIS_ERBB2_BREAST_TUMORS_65_DN
Systematic name M13715
Brief description 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].
Full description or abstract 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.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 15897883   Authors: Landis MD,Seachrist DD,Montaņez-Wiscovich ME,Danielpour D,Keri RA
Exact source Table 1: Decreased in tumors
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Organism Mus musculus
Contributed by Leona Saunders (MSigDB Team)
Source platform AFFY_MG_U74
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Version history 3.0: First introduced

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