CDK5 and its activator P35 in normal pituitary and in pituitary adenomas: relationship to VEGF expression.

CDK5 and its activator P35 in normal pituitary and in pituitary adenomas: relationship to VEGF expression.
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正常垂体和垂体腺瘤中的 CDK5 及其激活剂 P35:与 VEGF 表达的关系

DOI:
10.7150/ijbs.7770
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发表时间:
2014
影响因子:
9.2
通讯作者:
Zhang Y
Zhang Y
中科院分区:
生物学2区
文献类型:
--
作者:
Xie W;Wang H;He Y;Li D;Gong L;Zhang Y

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垂体瘤为单克隆腺瘤,约占颅内肿瘤的10-15%。细胞周期蛋白依赖性激酶5 (CDK5)调节神经系统中各种蛋白质和细胞过程的活性,但其在垂体腺瘤中的潜在作用尚不清楚。CDK5的激酶活性需要与激活蛋白p35(也称为CDK5激活因子1,p35)相关联。在这里,我们发现与p35相关的功能性CDK5存在于正常人类垂体和垂体肿瘤中。此外,垂体腺瘤中p35 mRNA和蛋白水平高于正常腺体,提示CDK5活性可能在垂体瘤中上调。抑制大鼠垂体细胞中CDK5活性,降低血管内皮生长因子(VEGF)的表达,VEGF是一种调节血管生成和血管生成的蛋白质。我们的研究结果表明,CDK5介导的VEGF表达的增加可能在垂体腺瘤的发展中起着至关重要的作用,罗斯科维汀和其他CDK5抑制剂可能是有用的抗癌药物。
Pituitary tumors are monoclonal adenomas that account for about 10-15% of intracranial tumors. Cyclin-dependent kinase 5 (CDK5) regulates the activities of various proteins and cellular processes in the nervous system, but its potential roles in pituitary adenomas are poorly understood. The kinase activity of CDK5 requires association with an activating protein, p35 (also known as CDK5 activator 1, p35). Here, we show that functional CDK5, associated with p35, is present in normal human pituitary and in pituitary tumors. Furthermore, p35 mRNA and protein levels were higher in pituitary adenomas than in the normal glands, suggesting that CDK5 activity might be upregulated in pituitary tumors. Inhibition of CDK5 activity in rat pituitary cells, reduced the expression of vascular endothelial growth factor (VEGF), a protein that regulates vasculogenesis and angiogenesis. Our results suggest that increased CDK5-mediated VEGF expression might play a crucial role in the development of pituitary adenomas, and that roscovitine and other CDK5 inhibitors could be useful as anticancer agents.
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发表时间: 2002-10-01
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