Centromere protein H is up-regulated in primary human colorectal cancer and its overexpression induces aneuploidy.
Chromosomal instability (CIN) has been recognized as a hallmark of human cancer and is caused by continuous chromosome missegregation during mitosis. Proper chromosome segregation requires a physical connection between spindle microtubules and centromeric DNA and this attachment occurs at proteinaceous structures called kinetochore. Several centromere proteins such as CENP-A and CENP-H are the fundamental components of the human active kinetochore, and inappropriate expression of the centromere proteins could be a major cause of CIN. We have previously shown that CENP-A was overexpressed in primary human colorectal cancer. In this study, we show that CENP-H was also up-regulated in all of 15 primary human colorectal cancer tissues as well as in CIN tumor cell lines. Surprisingly, transient transfection of CENP-H expression plasmid into the diploid cell line HCT116 remarkably induced aneupoidy. Moreover, CENP-H stable transfectant of mouse embryonic fibroblast/3T3 cell lines showed aberrant interphase micronuclei, characteristic of chromosome missegregation. In these CENP-H overexpressed cells, CENP-H completely disappeared from the centromere of mitotic chromosomes, which might be the cause of the chromosome segregation defect. These results suggest that the aberrant expression and localization of a kinetochore protein CENP-H plays an important role in the aneuploidy frequently observed in colorectal cancers.
Tomonaga
Takeshi
T
Department of Molecular Diagnosis (F8), Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan. tomonaga@faculty.chiba-u.jp
Matsushita
Kazuyuki
K
Ishibashi
Masumi
M
Nezu
Masahiko
M
Shimada
Hideaki
H
Ochiai
Takenori
T
Yoda
Kinya
K
Nomura
Fumio
F
D016475:3T3 Cells; D000782:Aneuploidy; D000818:Animals; D043171:Chromosomal Instability; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D014162:Transfection; D015854:Up-Regulation
C121933:CENPH protein, human; D002868:Chromosomal Proteins, Non-Histone