Protein kinase C θ (PKCθ) expression and constitutive activation in gastrointestinal stromal tumors (GISTs)
Protein kinase C θ (PKCθ) expression and constitutive activation in gastrointestinal stromal tumors (GISTs)
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DOI：
10.1158/0008-5472.can-04-0559
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发表时间：
2004-08-01
期刊：
影响因子：
11.2
通讯作者：
Fletcher, JA
中科院分区：
文献类型：
--
作者：
Duensing, A;Joseph, NE;Fletcher, JA
KIT的表达是胃肠道间质瘤(GIST)的一个关键诊断特征，几乎所有的GIST都表达致癌形式的KIT或PDGFRA受体酪氨酸激酶蛋白，作为甲磺酸伊马替尼的治疗靶点(Gleevec；诺华，巴塞尔，瑞士)。然而，在PDGFRA突变的GIST中，KIT的表达可能很低，这增加了误诊为其他类型肉瘤的可能性。我们报道，信号中间蛋白激酶C theta(PKCtheta)是GIST的诊断标记物，包括那些缺乏KIT表达和/或包含PDGFRA突变的GIST。PKCtheta在大多数GIST中被强烈激活，因此可能与KIT/PDGFRA一起作为新的治疗靶点。
KIT expression is a key diagnostic feature of gastrointestinal stromal tumors (GISTs), and virtually all of the GISTs express oncogenic forms of the KIT or PDGFRA receptor tyrosine kinase proteins, which serve as therapeutic targets of imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). However, KIT expression can be low in PDGFRA-mutant GISTs, increasing the likelihood of misdiagnosis as other types of sarcoma. We report that the signaling intermediate protein kinase C theta (PKCtheta) is a diagnostic marker in GISTs, including those that lack KIT expression and/or contain PDGFRA mutations. PKCtheta is strongly activated in most GISTs and hence may serve, along with KIT/PDGFRA, as a novel therapeutic target.