Mitotic Kinase Expression and Colorectal Cancer Progression

Katayama, Hiroshi; Ota, Takayo; Jisaki, Fumiko; Ueda, Yoshimichi; Tanaka, Takuji; Odashima, Shizuo; Suzuki, Fumio; Terada, Yasuhiko; Tatsuka, Masaaki

doi:10.1093/jnci/91.13.1160

Cited by 167 publications

(133 citation statements)

References 10 publications

Supporting

Mentioning

121

Contrasting

Unclassified

Order By: Relevance

“…1 Among these alterations, the dysregulation of the mechanisms responsible for cell segregation is frequently observed in malignant cells. 2 Recent evidence suggests a group of serine-threonine kinases, known as Aurora kinases, to have an important role in carcinogenesis as key regulators of mammalian mitosis, crucial for identical and exact segregation of genomic material during cell division.…”

Section: Introductionmentioning

confidence: 99%

“…4 Thus, it is not unexpected that these kinases have been described to be related with chromosomal instability, agressive growth and poor outcome in leukemia and in various malignancies like breast, bladder, ovarian, pancreatic and colon cancer. 1,[5][6][7][8] This group of kinases consists of three highly related kinases, known as AURKA (alias STK6/STK15/AurA), AURKB (alias STK12/STK5/AurB) and AURKC (alias STK13/AurC) in mammals. AURKA and -B are expressed in the majority of normal cell types.…”

Section: Introductionmentioning

confidence: 99%

“…4,9 The regulatory facets of AURKA and -B include centrosome duplication, mitotic spindle formation, mitotic checkpoint activation and cytokinesis. 1 Notwithstanding the fact that AURKA and -B vary from each other regarding the localization and time point of activation during mitosis, they regulate the cell-cycle progression in a coordinated manner. 9 AURKA is localized on chromosome 20q13, a region frequently amplified by tumors.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacogenetic profiling of Aurora kinase B is associated with overall survival in metastatic colorectal cancer

Pohl

Azuma²,

Zhang

et al. 2010

Pharmacogenomics J

View full text Add to dashboard Cite

Aurora kinases are conserved eukaryotic serine-threonine kinases, which serve as key regulators of mammalian mitosis. Several studies revealed a distinct correlation between inaccurate chromosome segregation, leading to chromosomal number instability, cancer progression and poor outcome. The aim of this study was to investigate the correlation of Aurora kinases A (AURKA) and B (AURKB) with overall survival (OS) by quantifying gene expression analysis and evaluation of single-nucleotide polymorphisms (SNPs) in human colorectal cancer samples and assessing the associations with clinicopathological features. We evaluated intratumoral gene expression levels and SNPs of AURKA and -B from 41 patients with metastatic colorectal cancer (mCRC). Patients with a high expression level of AURKB (41.28) lived significantly shorter (n ¼ 11, median OS ¼ 6.4 months, 95% confidence interval (CI): 3.0-14.5 months) compared with patients with a low expression level (p1.28) (n ¼ 30, median OS ¼ 18.4 months, 95% CI: 14.7-27.8 months, P ¼ 0.026, Wald's test). Patients harboring any G-allele in AURKB 885A4G showed a significantly decreased OS (P ¼ 0.05, log-rank test). We did not find any associations with clinicopathological variables and AURKA gene expression levels. Our results suggest a potential role for AURKB inhibition in patients with mCRC; thereby supporting its potential role as a target in mCRC.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacogenetic profiling of Aurora kinase B is associated with overall survival in metastatic colorectal cancer

Pohl

Azuma²,

Zhang

et al. 2010

Pharmacogenomics J

View full text Add to dashboard Cite

show abstract

“…28 A significant overexpression of Aurora-B has been described in human cancer cell lines, and a correlation between Aurora-B expression levels and Duke's grade in colorectal tumors has been described. 29,30 Concerning the thyroid tissue, only Aurora-B expression has been recently investigated in a single report and showed to be present in normal tissue and upregulated in undifferentiated thyroid cancer cells and tissues. 31 In our study, we analyzed the expression and cellular localization of all the 3 Aurora kinases in human cell lines derived from normal thyrocytes and different histotypes of thyroid tumors, including a benign follicular adenoma.…”

mentioning

confidence: 99%

Expression of Aurora kinases in human thyroid carcinoma cell lines and tissues

Ulisse

Delcros²,

Baldini

et al. 2006

Intl Journal of Cancer

View full text Add to dashboard Cite

The Aurora kinases are involved in the regulation of cell cycle progression, and alterations in their expression have been shown to associate with cell malignant transformation. In the present study, we demonstrated that human thyrocytes express all 3 Aurora kinases (A, B and C) at both protein and mRNA level and this expression is cell cycle-regulated. An increase in the protein level of the 3 kinases was found, with respect to normal human thyrocytes (HTU5), in the human cell lines derived from follicular (FTC-133), papillary (B-CPAP) and anaplastic (8305C) thyroid carcinomas, but not in cells derived from a follicular adenoma (HTU42). These observations were mirrored in RT-PCR experiments for Aurora-A and B. In contrast, Aurora-C mRNA levels were not significantly different among the different cell types analyzed, suggesting that posttranscriptional mechanism(s) modulate its expression. The expression at the protein level of all 3 Aurora kinases was significantly higher in 3 thyroid papillary carcinomas with respect to normal matched tissues obtained from the same patients. Similar modifications, at the mRNA level, could be observed in 7 papillary carcinoma tissues for Aurora-A and B, but not for Aurora-C. In conclusion, we demonstrated that normal human thyrocytes express all 3 members of the Aurora kinase family, and their expression is amplified in malignant thyroid cell lines and tissues. These results suggest that the Aurora kinases may play a relevant role in malignant thyroid cancers, and may represent a putative therapeutic target for thyroid neoplasms

show abstract

“…Indeed Aurora kinases are over-expressed in a number of cancers, and transfection studies have established AK-A as a bone fide oncogene [12,13,14,15]. Overexpression of AK-B also induces tumour formation [16,17]. AK-C has been found to be over-expressed in some cancer cell lines including HepG2, HUH7, MDA-MB-453 and HeLa.…”

Section: Aurora Kinases and Cancermentioning

confidence: 99%

An integrated pharmacokinetic–pharmacodynamic model for an Aurora kinase inhibitor

Kamei

Jackson

Zheleva

et al. 2010

J Pharmacokinet Pharmacodyn

View full text Add to dashboard Cite

The spindle assembly checkpoint is a cell cycle surveillance mechanism that ensures the proper separation of chromosomes prior to cell division at mitosis. Aurora kinases play critical roles in mitotic progression and hence small-molecule inhibitors of Aurora kinases have been developed as a new class of potential anticancer drugs. In this paper we present for the first time an integrated pharmacokinetic-pharmacodynamic model of the functional effects of CYC116 (a known inhibitor of Aurora kinases A and B) on the spindle assembly checkpoint. We use the model to simulate two common experimental systems: cell culture and p.o. dosing of mice and present predictions of the effects of CYC116 for a range of doses and drug scheduling regimes. The model reveals that a critical peak drug concentration is required to cause aberrant kinetochore-microtubule attachments. The model also predicts that provided this threshold concentration is exceeded, a high total oral dose causes a high number of aberrant attachments within any given damaged cell. However, the proportion of cells which enter anaphase with aberrant attachments is associated with the total length of time for which the plasma concentration is maintained above the threshold. Moreover, our model reveals that the length of prometaphase/metaphase is a nonlinear function of drug dose and this time period can be extended or shortened. Finally, a strong saturation effect on CYC116 efficacy is predicted by the model. We discuss how these predictions may have implications for further drug trials using CYC116 and other similar AK inhibitors.

show abstract

Mitotic Kinase Expression and Colorectal Cancer Progression

Cited by 167 publications

References 10 publications

Pharmacogenetic profiling of Aurora kinase B is associated with overall survival in metastatic colorectal cancer

Pharmacogenetic profiling of Aurora kinase B is associated with overall survival in metastatic colorectal cancer

Expression of Aurora kinases in human thyroid carcinoma cell lines and tissues

An integrated pharmacokinetic–pharmacodynamic model for an Aurora kinase inhibitor

Contact Info

Product

Resources

About