Gene Set: LABBE_WNT3A_TARGETS_DN

Standard name LABBE_WNT3A_TARGETS_DN
Systematic name M1837
Brief description Down-regulated genes in NMuMG cells (mammary epithelium) after stimulation with WNT3A [GeneID=89780].
Full description or abstract Transforming growth factor-beta (TGF-beta) and Wnt ligands function in numerous developmental processes, and alterations of both signaling pathways are associated with common pathologic conditions, including cancer. To obtain insight into the extent of interdependence of the two signaling cascades in regulating biological responses, we used an oligonucleotide microarray approach to identify Wnt and TGF-beta target genes using normal murine mammary gland epithelial cells as a model. Combination treatment of TGF-beta and Wnt revealed a novel transcriptional program that could not have been predicted from single ligand treatments and included a cohort of genes that were cooperatively induced by both pathways. These included both novel and known components or modulators of TGF-beta and Wnt pathways, suggesting that mutual feedback is a feature of the coordinated activities of the ligands. The majority of the cooperative targets display increased expression in tumors derived from either Min (many intestinal neoplasia) or mouse mammary tumor virus (MMTV)-Wnt1 mice, two models of Wnt-induced tumors, with nine of these genes (Ankrd1, Ccnd1, Ctgf, Gpc1, Hs6st2, IL11, Inhba, Mmp14, and Robo1) showing increases in both. Reduction of TGF-beta signaling by expression of a dominant-negative TGF-beta type II receptor in bigenic MMTV-Wnt1/DNIIR mice increased mammary tumor latency and was correlated with a decrease in expression of Gpc1, Inhba, and Robo1, three of the TGF-beta/Wnt cooperative targets. Our results indicate that the TGF-beta and Wnt/beta-catenin pathways are firmly intertwined and generate a unique gene expression pattern that can contribute to tumor progression.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17210685   Authors: Labbé E,Lock L,Letamendia A,Gorska AE,Gryfe R,Gallinger S,Moses HL,Attisano L
Exact source Table 1S: Wnt-repressed genes (Top 124 genes)
Related gene sets (show 5 additional gene sets from the source publication)

(show 1 gene sets from the same authors)
External links  
Organism Mus musculus
Contributed by Jessica Robertson (Broad Institute)
Source platform UnigeneIdentifiers
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.1: First introduced

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