A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers.
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.
Bischoff
J R
JR
SUGEN, Inc., Redwood City, California 94063, USA.
Anderson
L
L
Zhu
Y
Y
Mossie
K
K
Ng
L
L
Souza
B
B
Schryver
B
B
Flanagan
P
P
Clairvoyant
F
F
Ginther
C
C
Chan
C S
CS
Novotny
M
M
Slamon
D J
DJ
Plowman
G D
GD
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D064127:Aurora Kinases; D002453:Cell Cycle / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics*; D005347:Fibroblasts / Q000201:enzymology; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D005816:Genetic Complementation Test; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008938:Mitosis / Q000235:genetics; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D015854:Up-Regulation / Q000235:genetics
D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; D064127:Aurora Kinases; C576961:IPL1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases