A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers

被引:1079
作者
Bischoff, JR
Anderson, L
Zhu, YF
Mossie, K
Ng, L
Souza, B
Schryver, B
Flanagan, P
Clairvoyant, F
Ginther, C
Chan, CSM
Novotny, M
Slamon, DJ
Plowman, GD
机构
[1] SUGEN Inc, Redwood City, CA 94063 USA
[2] Univ Calif Los Angeles, Sch Med, Div Hematol Oncol, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA
[4] Univ Texas, Dept Microbiol, Austin, TX 78712 USA
关键词
20q13; amplicon; centrosome; colon cancer; oncogene; serine-threonine kinase;
D O I
10.1093/emboj/17.11.3052
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Genetic and biochemical studies in lower eukaryotes have identified several proteins that ensure accurate segregation of chromosomes. These include the Drosophila aurora and yeast Ipl1 kinases that are required for centrosome maturation and chromosome segregation. We have identified two human homologues of these genes, termed aurora1 and aurora2, that encode cell-cycle-regulated serine/threonine kinases. Here we demonstrate that the aurora2 gene maps to chromosome 20q13, a region amplified in a variety of human cancers, including a significant number of colorectal malignancies. We propose that aurora2 may be a target of this amplicon since its DNA is amplified and its RNA overexpressed, in more than 50% of primary colorectal cancers. Furthermore, overexpression of aurora2 transforms rodent fibroblasts. These observations implicate aurora2 as a potential oncogene in many colon, breast and other solid tumors, and identify centrosome-associated proteins as novel targets for cancer therapy.
引用
收藏
页码:3052 / 3065
页数:14
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