Antisense RNA inhibition of cathepsin L expression reduces tumorigenicity of malignant cells
Antisense RNA inhibition of cathepsin L expression reduces tumorigenicity of malignant cells
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DOI：
10.1016/s0959-8049(00)00014-9
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发表时间：
2000-04-01
影响因子：
8.4
通讯作者：
Vuorio, E
中科院分区：
文献类型：
--
作者：
Kirschke, H;Eerola, R;Vuorio, E
已知几种肿瘤形成细胞系过量产生溶酶体半胱氨酸肽酶组织蛋白酶 L。我们使用反义方法来研究抑制两种恶性细胞系（骨髓瘤 SP 细胞和 L 细胞）中组织蛋白酶 L 的过度表达是否会降低其致瘤潜力。将鼠组织蛋白酶 L 的两个不同 cDNA 片段以反义方向插入 pcDNA3 载体中，并用这些质粒构建体稳定转染 SP 和 L 细胞。表达反义转录物的几个所选克隆显示出组织蛋白酶 L 的 mRNA 水平和细胞内活性的特异性降低，以及分泌的组织蛋白酶 L 原的量大大减少。当在 Balb/c nu/nu 小鼠中进行测试时，与表达野生型水平的组织蛋白酶 L 活性的对照细胞相比，具有低组织蛋白酶 L 活性的细胞系表现出显着降低的肿瘤生长潜力。这一观察结果表明组织蛋白酶 L 是肿瘤生长的关键因素。 (C) 2000 年由爱思唯尔科学有限公司出版。保留所有权利。
Several tumour-forming cell lines are known to overproduce the lysosomal cysteine peptidase cathepsin L. We have used an antisense approach to investigate whether inhibition of cathepsin L overexpression in two malignant cell lines (myeloma SP cells and L cells) reduces their tumorigenic potential. Two different cDNA fragments of murine cathepsin L were inserted in the antisense direction into the pcDNA3 vector, and SP and L cells were stably transfected with these plasmid constructs. Several of the selected clones expressing the antisense transcript showed specific reduction of the mRNA level and the intracellular activity of cathepsin L, and a greatly diminished amount of secreted procathepsin L. When tested in Balb/c nu/nu mice, the cell lines with low cathepsin L activity exhibited a significantly decreased potential for tumour growth when compared with control cells expressing wild-type levels of cathepsin L activity. This observation suggests that cathepsin L is a critical factor in tumour growth. (C) 2000 Published by Elsevier Science Ltd. All rights reserved.