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

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Abstract

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.

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Acknowledgments

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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Authors and Affiliations

  1. Department of Tumor Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, Shizuoka, 431-3192, Japan

    Kazuya Shinmura, Nobuya Kurabe, Masanori Goto, Hidetaka Yamada, Hiroko Natsume & Haruhiko Sugimura

  2. Department of Surgery 2, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Hiroyuki Konno

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  1. Kazuya Shinmura
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  2. Nobuya Kurabe
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  7. Haruhiko Sugimura
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Correspondence to Kazuya Shinmura.

Additional information

The sequence data for a novel variant of PLK4 have been submitted to the DNA Data Bank of Japan (DDBJ) database (http://www.ddbj.nig.ac.jp/index-e.html) under accession number AB741646.

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Shinmura, K., Kurabe, N., Goto, M. et al. PLK4 overexpression and its effect on centrosome regulation and chromosome stability in human gastric cancer. Mol Biol Rep 41, 6635–6644 (2014). https://doi.org/10.1007/s11033-014-3546-2

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