Human Gene Set: HE_PTEN_TARGETS_UP

For the Mouse gene set with the same name, see HE_PTEN_TARGETS_UP

Standard name HE_PTEN_TARGETS_UP
Systematic name M1377
Brief description Genes up-regulated in the intestine after the tissue specific knockout of PTEN [GeneID=5728] by Cre-lox.
Full description or abstract Intestinal polyposis, a precancerous neoplasia, results primarily from an abnormal increase in the number of crypts, which contain intestinal stem cells (ISCs). In mice, widespread deletion of the tumor suppressor Phosphatase and tensin homolog (PTEN) generates hamartomatous intestinal polyps with epithelial and stromal involvement. Using this model, we have established the relationship between stem cells and polyp and tumor formation. PTEN helps govern the proliferation rate and number of ISCs and loss of PTEN results in an excess of ISCs. In PTEN-deficient mice, excess ISCs initiate de novo crypt formation and crypt fission, recapitulating crypt production in fetal and neonatal intestine. The PTEN-Akt pathway probably governs stem cell activation by helping control nuclear localization of the Wnt pathway effector beta-catenin. Akt phosphorylates beta-catenin at Ser552, resulting in a nuclear-localized form in ISCs. Our observations show that intestinal polyposis is initiated by PTEN-deficient ISCs that undergo excessive proliferation driven by Akt activation and nuclear localization of beta-catenin.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17237784   Authors: He XC,Yin T,Grindley JC,Tian Q,Sato T,Tao WA,Dirisina R,Porter-Westpfahl KS,Hembree M,Johnson T,Wiedemann LM,Barrett TA,Hood L,Wu H,Li L
Exact source Fig 2e: red in Mut
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Source species Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
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Version history 3.1: First introduced

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