Aurora B Overexpression Associates with the Thyroid Carcinoma Undifferentiated Phenotype and Is Required for Thyroid Carcinoma Cell Proliferation

Sorrentino, R; Libertini, Silvana; Pallante, P; Troncone, Giancarlo; Palombini, Lucio; Bavetsias, Vassilios; Spalletti-Cernia, Daniela; Laccetti, Paolo; Linardopoulos, Spiros; Chieffi, Paolo; Fusco, Alfredo; Portella, Giuseppe

doi:10.1210/jc.2004-1518

Cited by 187 publications

(144 citation statements)

References 37 publications

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“…In addition, the analysis related to the dedifferentiation process confirmed over-and underexpression of genes previously described to indicate poor prognosis for thyroid tumors (Rocha et al, 2003;Onda et al, 2004;Motti et al, 2005;Pallante et al, 2005;Sorrentino et al, 2005;Zou et al, 2005; Table 4). …”

Section: Discussionsupporting

confidence: 74%

Molecular profiling related to poor prognosis in thyroid carcinoma. Combining gene expression data and biological information

et al. 2007

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Undifferentiated and poorly differentiated thyroid tumors are responsible for more than half of thyroid cancer patient deaths in spite of their low incidence. Conventional treatments do not obtain substantial benefits, and the lack of alternative approaches limits patient survival. Additionally, the absence of prognostic markers for well-differentiated tumors complicates patient-specific treatments and favors the progression of recurrent forms. In order to recognize the molecular basis involved in tumor dedifferentiation and identify potential markers for thyroid cancer prognosis prediction, we analysed the expression profile of 44 thyroid primary tumors with different degrees of dedifferentiation and aggressiveness using cDNA microarrays. Transcriptome comparison of dedifferentiated and well-differentiated thyroid tumors identified 1031 genes with >2-fold difference in absolute values and false discovery rate of o0.15. According to known molecular interaction and reaction networks, the products of these genes were mainly clustered in the MAPkinase signaling pathway, the TGF-b signaling pathway, focal adhesion and cell motility, activation of actin polymerization and cell cycle. An exhaustive search in several databases allowed us to identify various members of the matrix metalloproteinase, melanoma antigen A and collagen gene families within the upregulated gene set. We also identified a prognosis classifier comprising just 30 transcripts with an overall accuracy of 95%. These findings may clarify the molecular mechanisms involved in thyroid tumor dedifferentiation and provide a potential prognosis predictor as well as targets for new therapies.

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Section: Discussionsupporting

confidence: 74%

Molecular profiling related to poor prognosis in thyroid carcinoma. Combining gene expression data and biological information

et al. 2007

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“…3 Beside the lack of amplification on gene level, several studies revealed an overexpression of mRNA and protein levels in several malignancies, associated with lymph node invasion, proliferation and metastasis. [14][15][16][17][18] AURKB belongs to the family of chromosomal passenger proteins and is essential for accurate chromosomal segregation and orientation, spindle assembly checkpoint, chromosome condensation, nuclear envelope formation and cytokinesis. 3,19,20 There is not much information available regarding polymorphisms in both genes.…”

Section: Introductionmentioning

confidence: 99%

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

Pohl

Azuma²,

Zhang

et al. 2010

Pharmacogenomics J

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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.

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“…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. We further extended the analysis of their expression to normal and papillary carcinoma thyroid tissues obtained following thyroidectomy.…”

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confidence: 99%

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

Ulisse

Delcros²,

Baldini

et al. 2006

Intl Journal of Cancer

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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

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Aurora B Overexpression Associates with the Thyroid Carcinoma Undifferentiated Phenotype and Is Required for Thyroid Carcinoma Cell Proliferation

Cited by 187 publications

References 37 publications

Molecular profiling related to poor prognosis in thyroid carcinoma. Combining gene expression data and biological information

Molecular profiling related to poor prognosis in thyroid carcinoma. Combining gene expression data and biological information

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

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