http://purl.uniprot.org/citations/20416302 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/20416302 | http://www.w3.org/2000/01/rdf-schema#comment | "Background & aimsCommensal bacteria can activate signaling by the Toll-like and interleukin-1 receptors (TLR and IL-1R) to mediate pathogenesis of inflammatory bowel diseases and colitis-associated cancer. We investigated the role of the single immunoglobulin IL-1 receptor-related (SIGIRR) molecule, a negative regulator of TLR and IL-1R signaling, as a tumor suppressor to determine whether SIGIRR controls cell-cycle progression, genetic instability, and colon tumor initiation by modulating commensal TLR signaling in the gastrointestinal tract.MethodsWe analyzed adenomatous polyposis coli (Apc)min/+/Sigirr-/-mice for polyps, microadenomas, and anaphase bridge index. Commensal bacteria were depleted from mice with antibiotics. Akt, mammalian target of rapamycin (mTOR), and beta-catenin pathways were examined by immunoblotting and immunohistochemistry. Loss of heterozygosity of Apc and expression of cytokines and proinflammatory mediators were measured by nonquantitative or quantitative polymerase chain reaction.ResultsApcmin/+/Sigirr-/-mice had increased loss of heterozygosity of Apc and microadenoma formation, resulting in spontaneous colonic polyposis, compared with Apcmin/+/Sigirr+/+ mice. The increased colonic tumorigenesis that occurred in the Apcmin/+/Sigirr-/-mice depended on the presence of commensal bacteria in the gastrointestinal tract. Cell proliferation and chromosomal instability increased in colon crypt cells of the Apcmin/+/Sigirr-/-mice. Akt, mTOR, and their substrates were hyperactivated in colon epithelium of Apcmin/+/Sigirr-/-mice in response to TLR or IL-1R ligands. Inhibition of the mTOR pathway by rapamycin reduced formation of microadenomas and polyps in the Apcmin/+/Sigirr-/-mice.ConclusionsSIGIRR acts as a tumor suppressor in the colon by inhibiting TLR-induced, mTOR-mediated cell-cycle progression and genetic instability."xsd:string |
http://purl.uniprot.org/citations/20416302 | http://purl.org/dc/terms/identifier | "doi:10.1053/j.gastro.2010.04.043"xsd:string |
http://purl.uniprot.org/citations/20416302 | http://purl.uniprot.org/core/author | "Li X."xsd:string |
http://purl.uniprot.org/citations/20416302 | http://purl.uniprot.org/core/author | "Zhou H."xsd:string |
http://purl.uniprot.org/citations/20416302 | http://purl.uniprot.org/core/author | "Yin W."xsd:string |
http://purl.uniprot.org/citations/20416302 | http://purl.uniprot.org/core/author | "Jacobson K."xsd:string |
http://purl.uniprot.org/citations/20416302 | http://purl.uniprot.org/core/author | "Khan M.A."xsd:string |
http://purl.uniprot.org/citations/20416302 | http://purl.uniprot.org/core/author | "Xiao H."xsd:string |
http://purl.uniprot.org/citations/20416302 | http://purl.uniprot.org/core/author | "Gulen M.F."xsd:string |
http://purl.uniprot.org/citations/20416302 | http://purl.uniprot.org/core/author | "Sham H.P."xsd:string |
http://purl.uniprot.org/citations/20416302 | http://purl.uniprot.org/core/author | "Vallance B.A."xsd:string |
http://purl.uniprot.org/citations/20416302 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
http://purl.uniprot.org/citations/20416302 | http://purl.uniprot.org/core/name | "Gastroenterology"xsd:string |
http://purl.uniprot.org/citations/20416302 | http://purl.uniprot.org/core/pages | "574-585"xsd:string |
http://purl.uniprot.org/citations/20416302 | http://purl.uniprot.org/core/title | "Loss of single immunoglobulin interlukin-1 receptor-related molecule leads to enhanced colonic polyposis in Apc(min) mice."xsd:string |
http://purl.uniprot.org/citations/20416302 | http://purl.uniprot.org/core/volume | "139"xsd:string |
http://purl.uniprot.org/citations/20416302 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/20416302 |
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