PLK4 overexpression and its effect on centrosome regulation and chromosome stability in human gastric cancer
PLK4 overexpression and its effect on centrosome regulation and chromosome stability in human gastric cancer
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DOI：
10.1007/s11033-014-3546-2
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发表时间：
2014-10-01
影响因子：
2.8
通讯作者：
Sugimura, Haruhiko
中科院分区：
文献类型：
--
作者：
Shinmura, Kazuya;Kurabe, Nobuya;Sugimura, Haruhiko
Polo样激酶4（PLK 4）是一种参与调节中心体复制的中心体蛋白。本研究旨在探讨PLK 4基因异常是否与胃癌的发生有关。首先，我们使用RT-PCR分析检测了7种胃癌细胞系和48种原发性胃癌中PLK 4 mRNA的表达状况。在57.1%（4/7）的胃癌细胞系中检测到PLK 4 mRNA表达上调，并且鉴定出具有外显子4但不具有外显子5的新型PLK 4变体。原发性胃癌中PLK 4 mRNA表达上调率为50.0%（24/48），差异有统计学意义（P值= 0.0139）。接下来，我们使用piggyBac转座子载体系统建立了能够诱导表达PLK 4的AGS胃癌细胞，并分别使用免疫荧光和FISH分析显示PLK 4过表达诱导中心体扩增和染色体不稳定性。此外，PLK 4过表达抑制初级纤毛形成。我们目前的研究结果表明，PLK 4在原发性胃癌的一个子集中上调，PLK 4过表达诱导中心体扩增和染色体不稳定性，并导致原发纤毛形成的抑制。
Polo-like kinase 4 (PLK4) is a centrosomal protein that is involved in the regulation of centrosome duplication. This study aimed to determine whether the genetic abnormality of PLK4 is involved in human gastric cancer. First, we examined the status of PLK4 mRNA expression in 7 gastric cancer cell lines and 48 primary gastric cancers using an RT-PCR analysis. The upregulation of PLK4 mRNA expression was detected in 57.1 % (4/7) of the gastric cancer cell lines, and a novel PLK4 variant with exon 4, but without exon 5, was identified. In the primary gastric cancers, the upregulation of PLK4 mRNA expression in the cancerous cells was detected in 50.0 % (24/48) of the cases, and this upregulation was statistically significant (P value = 0.0139). Next, we established AGS gastric cancer cells capable of inducibly expressing PLK4 using the piggyBac transposon vector system and showed that PLK4 overexpression induced centrosome amplification and chromosome instability using immunofluorescence and FISH analyses, respectively. Furthermore, PLK4 overexpression suppressed primary cilia formation. Our current findings suggested that PLK4 is upregulated in a subset of primary gastric cancers and that PLK4 overexpression induces centrosome amplification and chromosome instability and causes the suppression of primary cilia formation.