Differential expression of AURKA and AURKB genes in bone marrow stromal mesenchymal cells of myelodysplastic syndrome: correlation with G-banding analysis and FISH

Oliveira, Fábio Morato de; Lucena-Araújo, Antonio R.; Favarin, Maria do Carmo; Palma, Patrícia Vianna Bonini; Rego, Eduardo Magalhães; Falcão, Roberto Passetto; Covas, Dimas Tadeu; Fontes, Aparecida Maria

doi:10.1016/j.exphem.2012.10.009

Cited by 23 publications

(16 citation statements)

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“…Yoshida et al 32 studied the expression of AURKB gene in CD34+ cells from 64 patients with MDS using RT-PCR and detected an association of disease progression and advanced subtype (ie, refractory anaemia with excess blasts—refractory anaemia with excess blasts (RAEB) 1 and RAEB 2) with increased expression of AURKB. Oliveira et al 33 evaluated the gene expression of AURKB in a cytogenetically stratified population of mesenchymal stem cells (MSCs) from patients with MDS. These authors reported the presence of deregulated gene expression, although there were no significant differences between MSCs with normal versus abnormal karyotype.…”

Section: Discussionmentioning

confidence: 99%

Proteins of the mitotic checkpoint and spindle are related to chromosomal instability and unfavourable prognosis in patients with myelodysplastic syndrome

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Proteins of the mitotic checkpoint and spindle are related to chromosomal instability and unfavourable prognosis in patients with myelodysplastic syndrome

et al. 2015

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“…Potential candidate genes based on their reported differential expression in adult MDS-MSCs, i.e., AURKA, AURKB, SCF, G-CSF and GM-CSF (Santamaria et al, 2012;Ferrer et al, 2013;Zhao et al, 2012b;Oliveira et al, 2013), were specifically analyzed and no differences were observed comparing RCC-MSCs, RAEB(t)-MSCs and HC-MSCs. Similarly, a comparable expression level of CXCL12, Dicer1 and Drosha in pediatric MDS-MSCs versus HC-MSCs was confirmed by RT-PCR (data not shown).…”

Section: Gene and Protein Expressionsmentioning

confidence: 99%

Despite differential gene expression profiles pediatric MDS derived mesenchymal stromal cells display functionality in vitro

et al. 2015

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Pediatric myelodysplastic syndrome (MDS) is a heterogeneous disease covering a spectrum ranging from aplasia (RCC) to myeloproliferation (RAEB(t)). In adult-type MDS there is increasing evidence for abnormal function of the bone-marrow microenvironment. Here, we extensively studied the mesenchymal stromal cells (MSCs) derived from children with MDS. MSCs were expanded from the bone-marrow of 17 MDS patients (RCC: n=10 and advanced MDS: n=7) and pediatric controls (n=10). No differences were observed with respect to phenotype, differentiation capacity, immunomodulatory capacity or hematopoietic support. mRNA expression analysis by Deep-SAGE revealed increased IL-6 expression in RCC- and RAEB(t)-MDS. RCC-MDS MSC expressed increased levels of DKK3, a protein associated with decreased apoptosis. RAEB(t)-MDS revealed increased CRLF1 and decreased DAPK1 expressions. This pattern has been associated with transformation in hematopoietic malignancies. Genes reported to be differentially expressed in adult MDS-MSC did not differ between MSC of pediatric MDS and controls. An altered mRNA expression profile, associated with cell survival and malignant transformation, of MSC derived from children with MDS strengthens the hypothesis that the micro-environment is of importance in this disease. Our data support the understanding that pediatric and adult MDS are two different diseases. Further evaluation of the pathways involved might reveal additional therapy targets.

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“…78 Aurora-A overexpression is observed in CSC-enriched populations, including breast cancer, 68 ovarian cancer, 54 AML, 79 and mesenchymal stem cells (MSCs) from myelodysplastic syndromes (MDS) patients. 80 Consistent overexpression of Aurora-A in CSCs indicates a central role of Aurora-A in promoting cancer stem-like properties (e.g., therapyresistance, tumorigenesis, and EMT). Indeed, Aurora-A inhibition has been shown to impair stem-like functions in various malignancies including ovarian cancer, 54 AML, 79 CML, 42 breast cancer, 81 glioma, 82 and glioblastoma.…”

Section: Stemnessmentioning

confidence: 99%

Aurora‐A Kinase: A Potent Oncogene and Target for Cancer Therapy

Yan

Wang

et al. 2016

Medicinal Research Reviews

211

181

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The Aurora kinase family comprises three serine/threonine kinases, Aurora-A, -B and -C. Among these, Aurora-A and -B play central roles in mitosis, whereas Aurora-C executes unique roles in meiosis. Overexpression or gene amplification of Aurora kinases have been reported in a broad range of human malignancies, pointing to their role as potent oncogenes in tumorigenesis.Aurora kinases therefore represent promising targets for anticancer therapeutics. So far, a number of Aurora kinase inhibitors (AKIs) have been generated, of which some are currently undergoing clinical trials. Recent studies have unveiled novel unexpected functions of Aurora kinases during cancer development and the mechanisms underlying the anticancer actions of AKIs. In this review, we discuss the most recent advances in Aurora-A kinase research and targeted cancer therapy, focusing on the oncogenic roles and signaling pathways of Aurora-A kinases in contributing tumorigenesis, the recent preclinical and clinical AKI data and potential alternative routes for Aurora-A kinase inhibition.Key words: Aurora-A; Aurora kinase inhibitors (AKIs); targeted cancer therapy; mitosis; tumorigenesis 3 In mammals, the Aurora family of serine/threonine kinases consists of Aurora-A, -B and -C, which share a highly conserved catalytic domain containing auto-phosphorylating sites. The catalytic domain is flanked by a very short C-terminal tail and an N-terminal domain of variable lengths 1,2 . In the C-terminal regions of Auroras, there exists a short amino-acid peptide motif called "destruction box" (D-box). The D-box is recognized by the anaphase-promoting complex/cyclosome (APC/C) for degradation through the ubiquitin/proteasome-dependent pathway ( Fig. 1A). Despite their structural similarities, the expression patterns, cellular localization and physiological functions of these three Aurora kinases are largely distinct.Aurora-A and -B are commonly expressed in most cell types whereas Aurora-C is specially expressed in the testis. Both Aurora-A and -B play key roles in regulating cell-cycle progression from G2 through to cytokinesis. Aurora-C has a unique physiological role in spermatogenesis and functions as a chromosomal passenger protein similar to Aurora-B in mitosis 2 .Overexpression of Aurora-A and -B have been found in multiple types of cancer (Table 1), which function as oncogenes to promote tumorigenesis, providing potential targets for cancer therapy.However, comparatively little information is available regarding the roles of Aurora-C in cancer.In this review, we will focus on recent progress as well as the main unresolved issues associated with Aurora-A in cancer.4 1 FUNCTIONS OF AURORA-A In normal cells a. MitosisIn G1 phase, the level of Aurora-A is rarely detectable. During S phase, a small proportion of Aurora-A is first detected at centrosomes. At late G2 phase, Aurora-A accumulates evidently at centrosomes and becomes activated 3 . During prometaphase and metaphase, active Aurora-A localizes on bipolar spindles and spindle poles after...

show abstract

Differential expression of AURKA and AURKB genes in bone marrow stromal mesenchymal cells of myelodysplastic syndrome: correlation with G-banding analysis and FISH

Cited by 23 publications

References 30 publications

Proteins of the mitotic checkpoint and spindle are related to chromosomal instability and unfavourable prognosis in patients with myelodysplastic syndrome

Proteins of the mitotic checkpoint and spindle are related to chromosomal instability and unfavourable prognosis in patients with myelodysplastic syndrome

Despite differential gene expression profiles pediatric MDS derived mesenchymal stromal cells display functionality in vitro

Aurora‐A Kinase: A Potent Oncogene and Target for Cancer Therapy

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