Bischoff JR, Anderson L, Zhu Y, Mossie K, Ng L, Souza B, Schryver B, Flanagan P, Clairvoyant F, Ginther C, Chan CS, Novotny M, Slamon DJ, Plowman GDA homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J 17: 3052-3065

SUGEN, Inc., Redwood City, California 94063, USA.
The EMBO Journal (Impact Factor: 10.43). 07/1998; 17(11):3052-65. DOI: 10.1093/emboj/17.11.3052
Source: PubMed


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.

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Available from: Greg D Plowman, Oct 09, 2015
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    • "Aurora Kinase A is required for mitotic entry, chromosome alignment, and cytokinesis, and its abnormal function can result in aberrant cell division and aneuploidy [6]. AURKA protein overexpression and gene amplification have been frequently observed in colorectal cancers at various stages of tumor progression [7] [8] [9] [10]. Nishida et al [11] first demonstrated an increased copy number (ICN) of AURKA gene in 29% of colorectal tumors, and more recently, Zhang et al [12] reported ICN in 32% of advanced colorectal cancers. "
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    ABSTRACT: A crucial role for Aurora Kinase A (AURKA) gene has been demonstrated in the advanced steps of colorectal tumor progression. Little is known, however, about its role in the early phases of the adenoma-carcinoma sequence. Moreover, no data are currently available concerning AURKA involvement in the serrated tumorigenesis. Fluorescence in situ hybridization analysis and immunohistochemistry were used to assess gene copy number and protein expression in 40 colorectal adenomas, 20 cancerized adenomas, and 20 serrated polyps. An increased copy number was found either in adenomatous tissue or in early cancer in the vast majority of cancerized adenomas, but only in 5% of adenomas (P < .001). Protein expression strictly paralleled fluorescence in situ hybridization results. No changes in the gene copy number were observed in serrated polyps, regardless of their histotype and the presence of dysplasia, even if high percentages of immunostained cells were detected in all the subgroups. AURKA gene is associated with progressive colorectal adenomas but is uninvolved in the development of nonprogressive adenomas. The diploid status of the gene is maintained along the progression of serrated neoplasia. AURKA protein expression in serrated polyps is uncoupled from gene status and is likely to reflect apoptotic dysregulation.
    Human pathology 12/2014; 46(3). DOI:10.1016/j.humpath.2014.11.016 · 2.77 Impact Factor
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    • "However, whether Aurora kinases have a role in cancer initiation is still a matter of debate. It has been reported that the overexpression of either Aurora-A, Aurora-B, or Aurora-C induces cell malignant transformation [46–48]. In different studies, however, although the ability of Aurora-A or Aurora-B to potentiate Ras-induced transformation was demonstrated, the transforming ability of either Aurora-A or Aurora-B overexpression alone was not observed [49, 50]. "
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    ABSTRACT: Anaplastic thyroid cancers (ATC) are among the most aggressive human neoplasms with a dire prognosis and a median survival time of few months from the diagnosis. The complete absence of effective therapies for ATC renders the identification of novel therapeutic approaches sorely needed. Chromosomal instability, a feature of all human cancers, is thought to represent a major driving force in thyroid cancer progression and a number of mitotic kinases showing a deregulated expression in malignant thyroid tissues are now held responsible for thyroid tumor aneuploidy. These include the three members of the Aurora family (Aurora-A, Aurora-B, and Aurora-C), serine/threonine kinases that regulate multiple aspects of chromosome segregation and cytokinesis. Over the last few years, several small molecule inhibitors targeting Aurora kinases were developed, which showed promising antitumor effects against a variety of human cancers, including ATC, in preclinical studies. Several of these molecules are now being evaluated in phase I/II clinical trials against advanced solid and hematological malignancies. In the present review we will describe the structure, expression, and mitotic functions of the Aurora kinases, their implications in human cancer progression, with particular regard to ATC, and the effects of their functional inhibition on malignant cell proliferation.
    International Journal of Endocrinology 07/2014; 2014(3):816430. DOI:10.1155/2014/816430 · 1.95 Impact Factor
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    • "AURKA gene is mapped to chromosome 20q13 and encodes aurora kinase A, a cell cycle-regulated kinase that plays a role in tumor development and progression (Bischoff et al., 1998). AURKA over-expression was detected in several tumor types and cancer cell lines (Sen et al., 1997; Bischoff et al., 1998; Zhou et al., 1998), and was associated with poor prognosis in neuroblastoma (Shang et al., 2009) and stage III colorectal cancer (Lam et al., 2008). AURKA expression level was demonstrated as an independent predictor of metastatic outcome in GIST (Lagarde et al., 2012). "
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    ABSTRACT: Introduction: Synovial sarcoma (SynSa) is an aggressive mesenchymal tumor, comprising approximately 10% of all soft tissue sarcomas. Over half of SynSa patients develop metastasis or local recurrence, but the underlying molecular mechanisms of the aggressive clinical behavior remain poorly characterized. Materials and methods: Sixty-four frozen tumor specimens from 54 SynSa patients were subjected to array comparative genomic hybridization (aCGH) and gene expression profiling. The examined set of tumor specimens included 16 primary tumors from untreated patients who did not develop metastasis/local recurrence (SynSa1 group), 26 primary tumors from untreated patients who developed metastases or local recurrence during follow-up (SynSa2 group), and 22 metachronous metastatic/recurrent SynSa tumors (SynSa3 group). Results: AURKA and KIF18A, which play important roles in various mitotic events, were the two most up-regulated genes in SynSa2 and SynSa3 groups compared to the SynSa1 group. Expression profiles of SynSa2 and SynSa3 tumors did not show any significant differences. Analysis of genomic index (GI) based on aCGH profiles demonstrated that the SynSa1 group consisted of tumors with significantly less complex genomes compared to SynSa2 and SynSa3 groups. There was no significant difference in genome complexity between SynSa2 and SynSa3 tumors. Conclusions: Primary SynSa tumors from patients who develop metastases or local recurrence share common molecular features with metastatic/recurrent tumors. Presented data suggest that the aggressive clinical SynSa behavior is determined early in tumorigenesis and might be related to impaired regulation of mitotic mechanisms. This article is part of a Directed Issue entitled: Rare Cancers.
    The International Journal of Biochemistry & Cell Biology 05/2014; DOI:10.1016/j.biocel.2014.05.006 · 4.05 Impact Factor
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