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Human Sgo1 Down-regulation Leads to Chromosomal Instability in Colorectal Cancer
  1. Moriya Iwaizumi (iwaizumi{at}hama-med.ac.jp)
  1. Hamamatsu Univ Sch Med, Japan
    1. Kazuya Shinmura (kzshinmu{at}hama-med.ac.jp)
    1. Hamamatsu Univ Sch Med, Japan
      1. Hiroki Mori (moripath{at}akiha.hama-med.ac.jp)
      1. Hamamatsu Univ Sch Med, Japan
        1. Hidetaka Yamada (h-yamada{at}akiha.hama-med.ac.jp)
        1. Hamamatsu Univ Sch Med, Japan
          1. Masaya Suzuki (masaya{at}anpyo.or.jp)
          1. Hamamatsu Univ Sch Med, Japan
            1. Yasuhiko Kitayama (ykitayama{at}iuhw.ac.jp)
            1. International Univ Health Welfare Mita Hospital, Japan
              1. Hisaki Igarashi (hisaki{at}hama-med.ac.jp)
              1. Hamamatsu Univ Sch Med, Japan
                1. Toshio Nakamura (toshi38{at}hama-med.ac.jp)
                1. Hamamatsu Univ Sch Med, Japan
                  1. Hideaki Suzuki (suzuki39{at}jikei.ac.jp)
                  1. Jikei Univ Sch Med, Japan
                    1. Yoshinori Watanabe (ywatanab{at}iam.u-tokyo.ac.jp)
                    1. Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan
                      1. Akira Hishida (ahishida{at}hama-med.ac.jp)
                      1. Hamamatsu Univ Sch Med, Japan
                        1. Mutsuhiro Ikuma (ikuma{at}hama-med.ac.jp)
                        1. Hamamatsu Univ Sch Med, Japan
                          1. Haruhiko Sugimura (hsugimur{at}hama-med.ac.jp)
                          1. Hamamatsu Univ Sch Med, Japan

                            Abstract

                            Background: Chromosomal instability (CIN) is recognized as a hallmark of cancer and is caused by a spindle assembly checkpoint disorder or chromosome mis-segregation during mitosis. Although the recent identification of human shugoshin (hSgo1), an important player in proper chromosome segregation, has suggested involvement of hSgo1 in colorectal tumorigenesis, little is known about how it is involved.

                            Aims: To obtain information about the status of hSgo1 in human colorectal cancer.

                            Method/results: Among the 46 colorectal cancer cases, hSgo1 mRNA expression was decreased in the tumor tissue in comparison with the corresponding normal tissue (P=0.032). Human Sgo1 down-regulated tumors (T/N ratio<0.5) had preferential location on the left side large bowel rather than on the right side (P=0.012), and a higher variation of centromere numbers revealed by Fluorescence in situ hybridization (FISH). To assess the effects of hSgo1 down-regulation, we performed hSgo1 knockdown by transfecting the diploid HCT116 cell line with a short hairpin RNA expression vector. Human Sgo1 knockdown cells proliferated slowly because of both G2/M arrest and apoptosis (P<0.001), and marked of CIN in the form of aneuploidy (P<0.001) and micronuclei (P<0.005) were later observed in hSgo1 knockdown cells. Increased centrosome amplification (P<0.05), the presence of binucleated cells, and mitotic catastrophes were also noted in hSgo1 knockdown cells.

                            Conclusions: These findings suggest that hSgo1 down-regulated colorectal cancers have a clinicopathological character of CIN and hSgo1 down-regulation leads to CIN in colorectal cancer cells.

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