Hec1/Ndc80 is overexpressed in human gastric cancer and regulates cell growth
Hec1/Ndc80 is overexpressed in human gastric cancer and regulates cell growth
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Hec1/Ndc80 在人胃癌中过度表达并调节细胞生长
DOI：
10.1007/s00535-013-0809-y
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发表时间：
2014-03-01
影响因子：
6.3
通讯作者：
Liu, Bingya
中科院分区：
文献类型：
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作者：
Qu, Ying;Li, Jianfang;Liu, Bingya
背景细胞分裂异常引起的染色体不稳定性是导致胃癌异质性的主要原因，而异质性又使胃癌具有高度复杂和恶性的特征。Hec 1/Ndc 80在调节G2/M期的适当细胞分裂中是关键的。本研究的目的是探讨Hec 1在体外和体内对胃癌细胞生长的影响。方法使用Oncomine数据库分析人正常组织和癌组织中Hec 1的mRNA水平。采用实时荧光定量PCR和免疫组化方法检测胃癌组织中Hec 1 mRNA和蛋白的表达。通过Hec 1基因敲低和过表达研究Hec 1对细胞生长的影响。流式细胞仪分析细胞凋亡和细胞周期分布。结果Hec 1 mRNA和蛋白在包括胃癌在内的多种人类肿瘤组织中广泛表达。Hec 1基因敲低可显著抑制体外和体内胃癌细胞的生长，诱导细胞凋亡，并将细胞分裂阻滞在G2/M期。相反，Hec 1过表达在体内适度促进胃癌细胞生长。结论Hec 1在胃癌细胞的生长过程中起重要作用。Hec 1水平升高可能发生在胃肿瘤发生的早期阶段。
BackgroundChromosomal instability caused by abnormal cell division is a major cause of heterogeneity which evokes highly complex and malignant features of gastric cancer. Hec1/Ndc80 is critical in regulating proper cell division at the G2/M phase. The aim of our study is to investigate the in vitro and in vivo effects of Hec1 on gastric cancer cell growth.MethodsThe mRNA levels of Hec1 in human normal and cancer tissues were analyzed using the Oncomine database. Hec1 mRNA and protein levels in human gastric cancer tissues were analyzed by quantitative realtime-PCR and immunohistochemical staining, respectively. The effects of Hec1 on cell growth were explored by Hec1 knockdown and Hec1 overexpression. Apoptosis and cell cycle distributions were analyzed by flow cytometry. In vivo tumorigenicity was performed by engrafting tumor cells into nude mice.ResultsHec1 mRNA and protein were broadly overexpressed in many human cancers including gastric cancer. Hec1 knockdown dramatically suppressed gastric cancer cell growth in vitro and in vivo, induced apoptosis, and arrested cell division at the G2/M phase. On the contrary, Hec1 overexpression moderately promoted gastric cancer cell growth in vivo. Hec1 overexpression induced asymmetrical chromosome alignments, abnormal cell division, and thus rendered chromosomal instability.ConclusionsHec1 is critical in maintaining the in vitro and in vivo growth of gastric cancer cells. Elevated Hec1 levels may occur at the early stage of gastric tumorigenesis.