| http://purl.uniprot.org/citations/25973846 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25973846 | http://www.w3.org/2000/01/rdf-schema#comment | "Recently tumor necrosis factor receptor super family member 18 (TNFRSF18, also called GITR) has been identified as a novel tumor suppressor gene in Multiple Myeloma (MM), undergoing aberrant DNA methylation-mediated gene expression silencing. Furthermore, the expression of GITR blocks canonical NF-κB activation in MM cells in response to TNFα. Bortezomib, a proteasome inhibitor, can induce NF-κB activation, which may significantly influence the drug response in MM patients. In this study, we aim to elucidate if GITR status is associated with response to Bortezomib in MM cells through regulating GITR mediated NF-κB blockade. We found that GITR was significantly downregulated in MM patients and cell lines. Overexpression of GITR inhibited non-canonical NF-κB activation induced by TNFα. Moreover, NF-κB inhibitor induced apoptosis in GITR-deficient MM cells in response to TNFα. In addition, overexpression of GITR could inhibit Bortezomib-induced NF-κB activation and enhance the cytotoxicity of Bortezomib in GITR-deficient MM cell line (MM1.S). In contrast, knockdown of GITR attenuated the cytotoxic effect of Bortezomib on GITR proficient MM (RPMI) cell line and increased NF-κB activation. Finally, overexpression of GITR enhanced the sensitivity to Bortezomib in co-culture with bone marrow stromal cells and significantly reduced the tumor growth in MM1.S xenograft mice. In conclusion, we demonstrated that GITR expression can enhance the sensitivity to Bortezomib by inhibiting Bortezomib-induced NF-κB activation."xsd:string |
| http://purl.uniprot.org/citations/25973846 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0127334"xsd:string |
| http://purl.uniprot.org/citations/25973846 | http://purl.uniprot.org/core/author | "Li G."xsd:string |
| http://purl.uniprot.org/citations/25973846 | http://purl.uniprot.org/core/author | "Zhang X."xsd:string |
| http://purl.uniprot.org/citations/25973846 | http://purl.uniprot.org/core/author | "Shi D."xsd:string |
| http://purl.uniprot.org/citations/25973846 | http://purl.uniprot.org/core/author | "Zhao Y."xsd:string |
| http://purl.uniprot.org/citations/25973846 | http://purl.uniprot.org/core/author | "Zhang K."xsd:string |
| http://purl.uniprot.org/citations/25973846 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25973846 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/25973846 | http://purl.uniprot.org/core/pages | "e0127334"xsd:string |
| http://purl.uniprot.org/citations/25973846 | http://purl.uniprot.org/core/title | "Expression of GITR Enhances Multiple Myeloma Cell Sensitivity to Bortezomib."xsd:string |
| http://purl.uniprot.org/citations/25973846 | http://purl.uniprot.org/core/volume | "10"xsd:string |
| http://purl.uniprot.org/citations/25973846 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25973846 |
| http://purl.uniprot.org/citations/25973846 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25973846 |
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