Proteomic features of potential tumor suppressor NESG1 in nasopharyngeal carcinoma

Proteomic features of potential tumor suppressor NESG1 in nasopharyngeal carcinoma
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鼻咽癌潜在抑癌基因NESG1的蛋白质组学特征

DOI:
10.1002/pmic.201200146
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发表时间:
2012-11-01
期刊:
影响因子:
3.4
通讯作者:
Fang, Weiyi
Fang, Weiyi
中科院分区:
生物学3区
文献类型:
--
作者:
Liu, Zhen;Chen, Chao;Fang, Weiyi

文献摘要

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我们之前将最近修订的NESG1基因定义为鼻咽癌(NPC)的潜在肿瘤抑制因子。在这里,我们进一步使用蛋白质组学技术在鼻咽癌细胞中全面检测nesg1控制的蛋白质。蛋白质组学分析发现NESG1对26个蛋白的调控解除,Western blot分析发现enolase 1 (alpha) (ENO1)、热休克蛋白90kda β (Grp94)、member 1 (HSP90B1)和cathepsin D (CTSD)蛋白的表达存在差异。有趣的是,a-烯醇化酶(ENO1)是鼻咽癌中过表达的基因,在鼻咽癌细胞中被证实是nesg1调控的蛋白。过表达的ENO1不仅能恢复细胞增殖和细胞周期进程,还能拮抗NESG1对细胞周期调节因子p21和CCNA1表达的调控,并诱导NESG1过表达的鼻咽癌细胞中C-Myc、pRB和E2F1的表达。实时荧光定量PCR和免疫组化分析显示NESG1与ENO1在鼻咽癌组织中的表达呈负相关。我们的观察结果表明,ENO1下调在nesg1诱导的鼻咽癌细胞生长抑制中起重要作用。
We previously defined the recently revised NESG1 gene as a potential tumor suppressor in nasopharyngeal carcinoma (NPC). Here, we further used proteomics technology to globally examine NESG1-controlled proteins in NPC cells. Twenty-six proteins were found to be deregulated by NESG1 using proteomics analysis while enolase 1 (alpha) (ENO1), heat shock protein 90 kDa beta (Grp94), member 1 (HSP90B1), and cathepsin D (CTSD) proteins were differentially expressed by Western blot. Interestingly, a-enolase (ENO1), an overexpressed gene in NPC, was confirmed as a NESG1-regulated protein in NPC cells. Overexpressed ENO1 not only restored cell proliferation and cell-cycle progression, but also antagonized the regulation of NESG1 to cell-cycle regulators p21 and CCNA1 expression as well as induced the expression of C-Myc, pRB, and E2F1 in NESG1-ovexpressed NPC cells. Real-time PCR and immunohistochemistry analysis showed that NESG1 expression is negatively correlated with ENO1 expression in NPC tissues. Our observations suggest that ENO1 downregulation plays an important role in NESG1-induced growth inhibition of NPC cancer cells.