title: PLK4 overexpression and its effect on centrosome regulation and chromosome stability in human gastric cancer.
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.
authors: Department of Tumor Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, Shizuoka, 431-3192, Japan, kzshinmu@hama-med.ac.jp.
authors: Kazuya
authors: K
authors: Shinmura
authors: Nobuya
authors: N
authors: Kurabe
authors: Masanori
authors: M
authors: Goto
authors: Hidetaka
authors: H
authors: Yamada
authors: Hiroko
authors: H
authors: Natsume
authors: Hiroyuki
authors: H
authors: Konno
authors: Haruhiko
authors: H
authors: Sugimura
mesh_terms: D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D045744:Cell Line, Tumor; D018385:Centrosome / Q000378:metabolism*; D043171:Chromosomal Instability; D002923:Cilia / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D059368:RNA Isoforms; D012333:RNA, Messenger; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
chemical_list: D059368:RNA Isoforms; D012333:RNA, Messenger; C490219:PLK4 protein, human; D017346:Protein Serine-Threonine Kinases