Molecular Biology Reports

, Volume 41, Issue 10, pp 6635–6644 | Cite as

PLK4 overexpression and its effect on centrosome regulation and chromosome stability in human gastric cancer

  • Kazuya ShinmuraEmail author
  • Nobuya Kurabe
  • Masanori Goto
  • Hidetaka Yamada
  • Hiroko Natsume
  • Hiroyuki Konno
  • Haruhiko Sugimura


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.


Centrosome amplification Chromosome instability Gastric cancer PLK4 Primary cilia 



We are grateful to Dr. T. Niki (Jichi Medical University, Japan) and Dr. Y. Dobashi (Omiya Medical Center, Japan) for providing us with a part of lung cancer cell lines. We also grateful to Dr. E.A. Nigg (Max-Planck-Institute for Biochemistry, Germany; University of Basel, Switzerland) for providing us with GFP-PLK4 expression vector. We acknowledge Ms. K. Nagura and Mr. M. Koda (Hamamatsu University School of Medicine) for their technical assistance. This work was supported by grants from the MHLW (21-1), the JSPS (22590356, 25460476), the MEXT (221S0001), and the Smoking Research Foundation.


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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Kazuya Shinmura
    • 1
    Email author
  • Nobuya Kurabe
    • 1
  • Masanori Goto
    • 1
  • Hidetaka Yamada
    • 1
  • Hiroko Natsume
    • 1
  • Hiroyuki Konno
    • 2
  • Haruhiko Sugimura
    • 1
  1. 1.Department of Tumor PathologyHamamatsu University School of MedicineHamamatsuJapan
  2. 2.Department of Surgery 2Hamamatsu University School of MedicineHamamatsuJapan

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