Autor: |
Takahide, Ota, Shiho, Suto, Hiroshi, Katayama, Zhen-Bo, Han, Fumio, Suzuki, Masayo, Maeda, Mikio, Tanino, Yasuhiko, Terada, Masaaki, Tatsuka |
Rok vydání: |
2002 |
Předmět: |
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Zdroj: |
Cancer research. 62(18) |
ISSN: |
0008-5472 |
Popis: |
Phosphorylation of histone H3 at Ser-10 is required for maintenance of properchromosome dynamics during mitosis. AIM-1, a mammalian Ipl1/aurora kinase involved in H3 phosphorylation, is transcriptionally overexpressed in many tumor cell lines. Increased expression of the AIM-1 gene has been observed in human colorectal tumors of advanced grade and stage. Here we report that forced exogenous overexpression of AIM-1 in Chinese hamster embryo cells causes increased mitotic Ser-10 phosphorylation with concomitant induction of lagging chromosomes during mitosis. Lagging chromosomes could also be induced by transfection with mutated histone H3 (S10E), which is thought to maintain Ser-10 in the phosphorylated state. In the present study, chromosome number instability and increased tumor invasiveness were noted in constitutively AIM-1-overexpressing cells in vivo. Increased mitotic Ser-10 phosphorylation was also observed in various colorectal tumor cells with high AIM-1 expression levels. These data suggest that increased H3 histone phosphorylation as a result of AIM-1 overexpression is a major precipitating factor of chromosome instability and, thus, may play a role in carcinogenesis. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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