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首页> 外文期刊>Oncogene >Galanin and galanin receptor type 1 suppress proliferation in squamous carcinoma cells: activation of the extracellular signal regulated kinase pathway and induction of cyclin-dependent kinase inhibitors
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Galanin and galanin receptor type 1 suppress proliferation in squamous carcinoma cells: activation of the extracellular signal regulated kinase pathway and induction of cyclin-dependent kinase inhibitors

机译:1型甘丙肽和甘丙肽受体可抑制鳞状细胞癌细胞的增殖:激活细胞外信号调节激酶途径并诱导细胞周期蛋白依赖性激酶抑制剂

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Galanin receptor 1 (GALR1) maps to a common region of 18q loss in head and neck squamous cell carcinomas and is frequently inactivated by methylation. To investigate effects of GALR1 and its signaling pathways, we stably expressed hemaglutinin-tagged GALR1 in a human oral carcinoma cell line (UM-SCC-1-GALR1) that expresses no endogenous GALR1. In transfected cells, galanin induced activation of the extracellular-regulated protein kinase-1/2 (ERK1/2) and suppressed proliferation. Galanin stimulation mediated decreased expression of cyclin D1 and increased expression of the cyclin-dependent kinase inhibitors (CKI), p27Kip1 and p57Kip2. Pretreatment with the ERK1/2-specific inhibitor U0126 prevented these galanin-induced effects. Phosphatidylinositol 3-kinase (PI3K) pathway activation did not differ in UM-SCC-1-GALR1 and UM-SCC-1-mock cells after galanin treatment. Pertussis toxin and LY294002 inhibition demonstrated that galanin and GALR1 induce ERK1/2 activation via Gi, not the PI3K pathway-linked to the G subunit. Galanin and GALR1 also inhibit colony formation and tumor growth in vivo. Our results implicate GALR1, a Gi protein-coupled receptor, as a tumor suppressor gene that inhibits cell proliferation via ERK1/2 activation.
机译:甘丙肽受体1(GALR1)定位于头颈部鳞状细胞癌中常见的18q缺失区域,经常被甲基化灭活。为了研究GALR1的作用及其信号通路,我们在不表达内源GALR1的人口腔癌细胞系(UM-SCC-1-GALR1)中稳定表达了血凝素标记的GALR1。在转染的细胞中,甘丙肽诱导了细胞外调节蛋白激酶-1/2(ERK1 / 2)的活化并抑制了增殖。甘丙肽刺激介导的细胞周期蛋白D1的表达降低和细胞周期蛋白依赖性激酶抑制剂(CKI),p27Kip1和p57Kip2的表达增加。用ERK1 / 2特异性抑制剂U0126进行预处理可预防这些甘丙肽诱导的作用。甘丙肽处理后,UM-SCC-1-GALR1和UM-SCC-1-模拟细胞的磷脂酰肌醇3激酶(PI3K)途径活化没有差异。百日咳毒素和LY294002抑制作用表明甘丙肽和GALR1通过Gi诱导ERK1 / 2激活,而不是与G亚基相连的PI3K途径。甘丙肽和GALR1在体内也抑制菌落形成和肿瘤生长。我们的研究结果表明,Gal1蛋白偶联受体GALR1是一种抑癌基因,可通过ERK1 / 2激活抑制细胞增殖。

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