| pubmed-article:18521081 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18521081 | lifeskim:mentions | umls-concept:C1416655 | lld:lifeskim |
| pubmed-article:18521081 | lifeskim:mentions | umls-concept:C0238198 | lld:lifeskim |
| pubmed-article:18521081 | lifeskim:mentions | umls-concept:C0033640 | lld:lifeskim |
| pubmed-article:18521081 | lifeskim:mentions | umls-concept:C0017262 | lld:lifeskim |
| pubmed-article:18521081 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:18521081 | lifeskim:mentions | umls-concept:C1690540 | lld:lifeskim |
| pubmed-article:18521081 | lifeskim:mentions | umls-concept:C1514485 | lld:lifeskim |
| pubmed-article:18521081 | lifeskim:mentions | umls-concept:C2911684 | lld:lifeskim |
| pubmed-article:18521081 | lifeskim:mentions | umls-concept:C0185117 | lld:lifeskim |
| pubmed-article:18521081 | pubmed:issue | 42 | lld:pubmed |
| pubmed-article:18521081 | pubmed:dateCreated | 2010-1-25 | lld:pubmed |
| pubmed-article:18521081 | pubmed:abstractText | Oncogenic KIT or PDGFRA receptor tyrosine kinase mutations are compelling therapeutic targets in gastrointestinal stromal tumors (GISTs), and the KIT/PDGFRA kinase inhibitor, imatinib, is standard of care for patients with metastatic GIST. However, most of these patients eventually develop clinical resistance to imatinib and other KIT/PDGFRA kinase inhibitors and there is an urgent need to identify novel therapeutic strategies. We reported previously that protein kinase C-theta (PKCtheta) is activated in GIST, irrespective of KIT or PDGFRA mutational status, and is expressed at levels unprecedented in other mesenchymal tumors, therefore serving as a diagnostic marker of GIST. Herein, we characterize biological functions of PKCtheta in imatinib-sensitive and imatinib-resistant GISTs, showing that lentivirus-mediated PKCtheta knockdown is accompanied by inhibition of KIT expression in three KIT+/PKCtheta+ GIST cell lines, but not in a comparator KIT+/PKCtheta- Ewing's sarcoma cell line. PKCtheta knockdown in the KIT+ GISTs was associated with inhibition of the phosphatidylinositol-3-kinase/AKT signaling pathway, upregulation of the cyclin-dependent kinase inhibitors p21 and p27, antiproliferative effects due to G(1) arrest and induction of apoptosis, comparable to the effects seen after direct knockdown of KIT expression by KIT short-hairpin RNA. These novel findings highlight that PKCtheta warrants clinical evaluation as a potential therapeutic target in GISTs, including those cases containing mutations that confer resistance to KIT/PDGFRA kinase inhibitors. | lld:pubmed |
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| pubmed-article:18521081 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18521081 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18521081 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:18521081 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18521081 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:18521081 | pubmed:issn | 1476-5594 | lld:pubmed |
| pubmed-article:18521081 | pubmed:author | pubmed-author:VigR GRG | lld:pubmed |
| pubmed-article:18521081 | pubmed:author | pubmed-author:SunFF | lld:pubmed |
| pubmed-article:18521081 | pubmed:author | pubmed-author:FletcherJ AJA | lld:pubmed |
| pubmed-article:18521081 | pubmed:author | pubmed-author:DemetriG DGD | lld:pubmed |
| pubmed-article:18521081 | pubmed:author | pubmed-author:FletcherC D... | lld:pubmed |
| pubmed-article:18521081 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:18521081 | pubmed:day | 18 | lld:pubmed |
| pubmed-article:18521081 | pubmed:volume | 27 | lld:pubmed |
| pubmed-article:18521081 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:18521081 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:18521081 | pubmed:pagination | 5624-34 | lld:pubmed |
| pubmed-article:18521081 | pubmed:dateRevised | 2011-5-5 | lld:pubmed |
| pubmed-article:18521081 | pubmed:meshHeading | pubmed-meshheading:18521081... | lld:pubmed |
| pubmed-article:18521081 | pubmed:meshHeading | pubmed-meshheading:18521081... | lld:pubmed |
| pubmed-article:18521081 | pubmed:meshHeading | pubmed-meshheading:18521081... | lld:pubmed |
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| pubmed-article:18521081 | pubmed:meshHeading | pubmed-meshheading:18521081... | lld:pubmed |
| pubmed-article:18521081 | pubmed:meshHeading | pubmed-meshheading:18521081... | lld:pubmed |
