Tumor suppressor ING4 overexpression contributes to proliferation and invasion inhibition in gastric carcinoma by suppressing the NF-κB signaling pathway
Tumor suppressor ING4 overexpression contributes to proliferation and invasion inhibition in gastric carcinoma by suppressing the NF-κB signaling pathway
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DOI：
10.1007/s11033-013-2675-3
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发表时间：
2013-10-01
影响因子：
2.8
通讯作者：
Ren, Xuequn
中科院分区：
文献类型：
--
作者：
Li, Shijie;Fan, Tianli;Ren, Xuequn
越来越多的证据表明，生长抑制因子4（Inhibitor of growth 4，ING 4）在多种肿瘤的发生、发展中起着关键作用，但其在胃癌中的确切作用尚不清楚。本研究通过检测胃癌组织和细胞中ING 4的表达水平，初步探讨ING 4在胃癌增殖和侵袭中的作用。结果表明，胃癌组织和细胞中ING 4 mRNA和蛋白的表达均明显低于正常组织和细胞（P < 0.05）。稳定表达ING 4的胃癌细胞ING 4水平明显高于未转染组和空载体组（P < 0.05）。ING 4在胃癌细胞系MKN-28、SGC-7901和MKN-45中的表达水平升高，可抑制胃癌细胞的增殖和侵袭。其中，ING 4水平的升高明显下调p65、p-I κ B α、MMP-9和uPA蛋白表达，上调I κ B α蛋白表达。我们的研究结果表明，ING 4水平升高介导的增殖和侵袭抑制可能与NF-κ B信号通路的抑制密切相关。
There is growing evidence that inhibitor of growth 4 (ING4) plays a pivotal role in development and progression of multiple different tumors; however, its precise function in gastric carcinoma remains to be elucidated. In the present study, we investigated ING4 level in gastric carcinoma tissues and cells, and preliminarily elucidated the role of ING4 in the proliferation and invasion of gastric carcinoma. The results demonstrated that expressions of ING4 mRNA and protein in gastric carcinoma tissues and cells were significantly lower than those in normal tissues and cells (P < 0.05). ING4 level in gastric carcinoma cells stably expressing ING4 was markedly higher than those in untreated group and empty vector pcDNA3.1 group (P < 0.05). Elevated ING4 level resulted in the inhibition of proliferation and invasion in three of gastric carcinoma cell lines MKN-28, SGC-7901 and MKN-45. Most notably, increased ING4 level evidently evoked the down-regulation of p65, p-I kappa B alpha, MMP-9 and uPA proteins and the up-regulation of I kappa B alpha protein. Our results presented herein suggest that ING4 level elevation mediated proliferation and invasion inhibition may be tightly associated with the suppression of NF-kappa B signaling pathway.