Overexpression and mistargeting of centromere protein-A in human primary colorectal cancer.
Aneuploidy is the hallmark of many human cancers. Recent work has strongly suggested that chromosome missegregation during mitosis is the main cause of aneuploidy and contributes to oncogenesis. Centromere protein (CENP)-A is the centromere-specific histone-H3-like variant essential for centromere structure and function. It plays a central role in the assembly of the protein complex, termed kinetochore, which is indispensable for equal chromosome segregation. In this study, we demonstrate that the kinetochore protein CENP-A was overexpressed in all of 11 primary human colorectal cancer tissues. CENP-A mRNA was also up-regulated, indicating that overexpression of CENP-A occurred at the transcriptional level. Immunostaining with anti-CENP-A antibodies showed increased CENP-A signals in the tumor cells. Moreover, coimmunostaining of CENP-B, a centromere-associated DNA binding protein, with CENP-A showed mistargeting of CENP-A to noncentromeric chromatin in the tumor cells. These results suggest that overexpression of CENP-A could play an important role for aneuploidy in colorectal cancers.
Tomonaga
Takeshi
T
Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan. tomonaga@med.m.chiba-u.ac.jp
Matsushita
Kazuyuki
K
Yamaguchi
Seiko
S
Oohashi
Tatsuya
T
Shimada
Hideaki
H
Ochiai
Takenori
T
Yoda
Kinya
K
Nomura
Fumio
F
D000782:Aneuploidy; D001324:Autoantigens / Q000235:genetics; D000076247:Centromere Protein A; D051936:Centromere Protein B; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D002874:Chromosome Mapping; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology / Q000601:surgery; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D004268:DNA-Binding Proteins; D006801:Humans; D009367:Neoplasm Staging; D012004:Rectal Neoplasms / Q000235:genetics / Q000473:pathology / Q000601:surgery; D014407:Tumor Cells, Cultured
D001324:Autoantigens; C000619700:CENPA protein, human; C497926:CENPB protein, human; D000076247:Centromere Protein A; D051936:Centromere Protein B; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins