Gene Set: PANGAS_TUMOR_SUPPRESSION_BY_SMAD1_AND_SMAD5_DN

Standard name PANGAS_TUMOR_SUPPRESSION_BY_SMAD1_AND_SMAD5_DN
Systematic name M2186
Brief description Genes down-regulated in ovarian tumors from mouse models for the BMP SMAD signaling (gonad specific double knockout of SMAD1 and SMAD5 [GeneID=4086] [GeneID=4090]).
Full description or abstract The transforming growth factor beta (TGFbeta) family has critical roles in the regulation of fertility. In addition, the pathogenesis of some human cancers is attributed to misregulation of TGFbeta function and SMAD2 or SMAD4 mutations. There are limited mouse models for the BMP signaling SMADs (BR-SMADs) 1, 5, and 8 because of embryonic lethality and suspected genetic redundancy. Using tissue-specific ablation in mice, we deleted the BR-SMADs from somatic cells of ovaries and testes. Single conditional knockouts for Smad1 or Smad5 or mice homozygous null for Smad8 are viable and fertile. Female double Smad1 Smad5 and triple Smad1 Smad5 Smad8 conditional knockout mice become infertile and develop metastatic granulosa cell tumors. Male double Smad1 Smad5 conditional knockout mice are fertile but demonstrate metastatic testicular tumor development. Microarray analysis indicated significant alterations in expression of genes related to the TGFbeta pathway, as well as genes involved in infertility and extracellular matrix production. These data strongly implicate the BR-SMADs as part of a critical developmental pathway in ovaries and testis that, when disrupted, leads to malignant transformation.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17967875   Authors: Pangas SA,Li X,Umans L,Zwijsen A,Huylebroeck D,Gutierrez C,Wang D,Martin JF,Jamin SP,Behringer RR,Robertson EJ,Matzuk MM
Exact source Table 1S
Related gene sets (show 1 additional gene sets from the source publication)

(show 26 gene sets from the same authors)
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Organism Mus musculus
Contributed by Arthur Liberzon (Broad Institute)
Source platform SEQ_ACCESSION
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Version history 3.1: First introduced

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