Matrix metalloproteinase 11 depletion inhibits cell proliferation in gastric cancer cells

Matrix metalloproteinase 11 depletion inhibits cell proliferation in gastric cancer cells
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DOI:
10.1016/j.bbrc.2004.11.027
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发表时间:
2005-01-14
影响因子:
3.1
通讯作者:
Lu, YY
Lu, YY
中科院分区:
生物学4区
文献类型:
--
作者:
Deng, H;Guo, RF;Lu, YY

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本课题组前期研究发现,基质金属蛋白酶11(MMP 11)在胃癌细胞株和原发灶中高表达。为了揭示MMP 11的表达与胃癌细胞生物学特性的相关性,本研究利用基于载体的RNA干扰技术,构建了针对MMP 11 mRNA的发夹型小干扰RNA(siRNA)重组质粒。RT-PCR和Western blotting分析表明,重组质粒稳定转染胃癌细胞BGC 823后,MMP 11的mRNA和蛋白表达均被特异性地清除。siRNA处理的细胞表现出显着降低的生长能力相比,模拟转染和亲本BGC 823细胞。此外,MMP 11缺陷细胞在软琼脂中的集落形成明显受到抑制,在裸小鼠体内的致瘤性也明显降低。这些结果为MMP 11的功能提供了新的见解,并表明MMP 11可能在控制GC细胞增殖和肿瘤发展中发挥重要作用。(C)2004年爱思唯尔公司All rights reserved.
Our previous study has shown that matrix metalloproteinase 11 (MMP11) is highly expressed in tumor cell lines and primary tumor of gastric cancer (GC). In order to reveal the correlation between expression of MMP11 and biological features of GC cell, we have constructed the recombinant plasmids producing hairpin small interfering RNA (siRNA) to target MMP11 mRNA using a vector-based RNA interference technology. Stable transfection of recombinants into GC cell line BGC823 specifically depleted the mRNA and protein of MMP11 as demonstrated by RT-PCR and Western blotting analysis. The siRNA-treated cells exhibited significantly decreased growth ability compared with mock transfectants and parental BGC823 cells. Furthermore, colony formation of MMP11 deficient cells was dramatically inhibited in soft agar and tumorigenicity was reduced in nude mice, respectively. These results provide new insights into the function of MMP11 and suggest that MMP11 may play an important role in the control of cell proliferation and tumor development in GC. (C) 2004 Elsevier Inc. All rights reserved.