Centromere protein H is up-regulated in primary human colorectal cancer and its overexpression induces aneuploidy.

Abstract	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.
Authors	Takeshi Tomonaga, Kazuyuki Matsushita, Masumi Ishibashi, Masahiko Nezu, Hideaki Shimada, Takenori Ochiai, Kinya Yoda, Fumio Nomura
Journal	Cancer research (Cancer Res) Vol. 65 Issue 11 Pg. 4683-9 (Jun 01 2005) ISSN: 0008-5472 [Print] United States
PMID	15930286 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	CENPH protein, human Chromosomal Proteins, Non-Histone
Topics	3T3 Cells Aneuploidy Animals Chromosomal Instability Chromosomal Proteins, Non-Histone (biosynthesis, genetics) Colorectal Neoplasms (genetics, metabolism) Gene Expression Regulation, Neoplastic Humans Mice Transfection Up-Regulation

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