Endothelin system in oral squamous carcinoma cells: Specific siRNA targeting of ECE-1 blocks cell proliferation
Endothelin system in oral squamous carcinoma cells: Specific siRNA targeting of ECE-1 blocks cell proliferation
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DOI：
10.1002/ijc.21525
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发表时间：
2006-04-01
影响因子：
6.4
通讯作者：
Usmani, BA
中科院分区：
文献类型：
--
作者：
Awano, S;Dawson, LA;Usmani, BA
本研究重点关注人口腔鳞状细胞癌 (SCC) 细胞的内皮素轴。我们研究了内皮素-1 (ET-1)、其受体（内皮素-A 受体 (ETAR) 和内皮素-B 受体 (ETBR)）及其特异性转换酶的亚型（ECE-1a、1b、1c）的表达和分布，并报告了它们对细胞增殖的相对影响。我们还研究了 ECE 特异性抑制剂 (ECE-1) 和针对 ECE-1 基因的 siRNA 对 SCC 细胞增殖的影响。我们观察到口腔鳞状细胞癌细胞中ET-1、ETAR、ETBR和所有内皮素转换酶-1（ECE-1）亚型的表达，但与正常人表皮角质形成细胞相比，仅ET-1、ETBR和ECE-1的表达增加。 ET-I单独刺激口腔SCC细胞的增殖。 ETAR 或 ETBR 的拮抗剂抑制 ET-1 介导的增殖。 ECE siRNA 处理后 ECE-1 表达降低，从而减少 SCC 细胞增殖。通过用 ECE-i 抑制 ECE 活性也观察到了抗增殖作用。总之，本研究表明，口腔鳞状细胞癌细胞内皮素系统的调节可能为口腔癌提供一种新的治疗方案。 (c) 2005 年 Wiley-Liss, Inc.
The present study focused on the endothelin axis in human oral squamous cell carcinoma (SCC) cells. We investigated the expression and distribution of endothelin-1 (ET-1), its receptors (endothelin-A receptor (ETAR) and endothelin-B receptor (ETBR)) and isoforms of its specific converting enzyme (ECE-1a, 1b, 1c) and the report on their relative influences on cell proliferation. We also investigated the effect of an ECE-specific inhibitor (ECE-1) and siRNA targeting of the ECE-1 gene on SCC cell proliferation. We observed the expression of ET-1, ETAR, ETBR and all endothelin-converting enzyme-1 (ECE-1) isoforms in oral SCC cells, but only the expression of ET-1, ETBR and ECE-1 was increased when compared to normal human epidermal keratinocytes. ET-I alone stimulated proliferation of oral SCC cells. Antagonists of either ETAR or ETBR inhibited ET-1-mediated proliferation. Decreased ECE-1 expression after ECE siRNA treatment reduced SCC cell proliferation. Antiproliferative effects were also observed by inhibiting ECE activity with ECE-i. In conclusion, the present study demonstrates that modulation of the endothelin system in oral SCC cells might provide a novel therapeutic protocol for oral cancer. (c) 2005 Wiley-Liss, Inc.