Upregulation of the cysteine protease inhibitor, cystatin SN, contributes to cell proliferation and cathepsin inhibition in gastric cancer
Upregulation of the cysteine protease inhibitor, cystatin SN, contributes to cell proliferation and cathepsin inhibition in gastric cancer
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DOI：
10.1016/j.cca.2009.05.008
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发表时间：
2009-08-11
影响因子：
5
通讯作者：
Lee, Hee Gu
中科院分区：
文献类型：
--
作者：
Choi, Eun Hwa;Kim, Jong-Tae;Lee, Hee Gu
工作背景：半胱氨酸蛋白酶如组织蛋白酶是广泛分布的蛋白水解酶，并在其活性位点与半胱氨酸蛋白酶抑制剂形成紧密的等摩尔复合物。在半胱氨酸蛋白酶抑制剂中，编码半胱氨酸蛋白酶抑制剂SN的CST 1是2型唾液半胱氨酸蛋白酶抑制剂家族的成员，其存在于多种流体和分泌物中，包括血浆、泪液和唾液。方法：采用RT-PCR方法检测15例胃癌组织中CST 1的表达水平，并与正常对照组比较。免疫组化及临床病理分析。结果：胃癌组织中CST 1表达明显高于癌旁组织，且与pTNM分期相关（p = 0.044）。结论：CST 1可能与胃癌的发生密切相关，并对半胱氨酸蛋白酶的蛋白水解活性有调节作用。皇冠版权所有（C）2009年出版的爱思唯尔B. V.保留所有权利。
Background: Cysteine proteases like cathepsins are widely distributed proteolytic enzymes and form tight equimolar complexes with cystatins at their active sites. Among cystatins, CST1, encoding cystatin SN, is a member of the type 2 salivary cystatin family found in a variety of fluids and secretions, including plasma, tears, and saliva. CST1 was identified as an upregulated gene in gastric cancer tissues compared to noncancerous regions using our Affymetrix GeneChip microarray.Methods: The upregulation of CST1 in gastric cancer was analyzed using RT-PCR (n = 15). immnohistochemistry, and clinicopathological (n = 77) analysis. CST1-siRNA was used for the suppression of CST1 gene expression and cathepsin proteolytic activity was assayed.Results: CST1 was upregulated in cancerous lesions of gastric cancer tissues compared to noncancerous regions and clinicopathological analysis showed a significant correlation between high expression of CST1 and pTNM stage (p = 0.044). In CST1-siRNA transfected cells, cell proliferation was reduced and the proteolytic activity of cathepsins was increased.Conclusions: CST1 might be highly involved in gastric tumorigenesis and regulate the proteolytic activity of cysteine proteases. Crown Copyright (C) 2009 Published by Elsevier B.V. All rights reserved.