Analysis of abnormal signaling through KIT and PDGFRA in development of gastrointestinal stromal tumors

我们建立了一个人源性多发性胃肠道间质瘤模型小鼠，该模型小鼠具有c-kit基因外显子17型突变。杂合子和纯合子模型小鼠具有盲肠GIST样肿瘤和胃和结肠的Cajal间质细胞增生。这些表型与先前报道的c-kit基因11号外显子或13号外显子突变模型小鼠的表型相似。一种分子靶向药物，伊马替尼，抑制组成型激活突变KIT给予模型小鼠，我们观察到肿瘤生长和KIT激活的抑制。我们还研究了另一种分子靶向药物尼洛替尼（nilotinib）对肿瘤生长和KIT激活的影响，目前正在准备手稿。

We made a model mouse of human family with multiple gastrointestinal stromal tumors and germline exon 17-type c-kit gene mutation. The heterozygous and homozygous model mice had a cecal GIST-like tumor and hyperplasia of interstitial cells of Cajal at stomach and colon. The phenotypes were similar with those observed in previously reported model mice with exon 11 or exon 13 c-kit gene mutation. A molecular targeted drug, imatinib, which inhibits constitutively activated mutant KIT was given to the model mice, and we observed inhibition of both tumor growth and KIT activation. We also examined an effect of another molecular targeted drug, nilotinib, which inhibits constitutively activated mutant KIT on tumor growth and KIT activation, and now the manuscript is in preparation.