Comparative immunohistochemical analysis of aurora-A and aurora-B expression in human glioblastomas. Associations with proliferative activity and clinicopathological features

Samaras, Vassilis; Stamatelli, Angeliki; Samaras, Efstathios; Arnaoutoglou, Christos; Arnaoutoglou, Marianthi; Stergiou, Ioanna Ε.; Konstantopoulou, Paraskevi; Varsos, Vassilis; Karameris, Andreas; Barbatis, Calypso

doi:10.1016/j.prp.2009.06.011

Cited by 23 publications

(18 citation statements)

References 36 publications

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“…Wang et al reported that overexpression of Aurora A kinase promotes tumor cell proliferation and inhibits apoptosis in esophageal squamous cell carcinoma cell line (40). Besides, associations of overexpression of Aurora A and cell proliferation were detected in glioblastoma patients (41). In our study, by FCM, PI staining, TUNEL and Ki-67 immunostaining, increased apoptosis and reduced cell proliferation were detected after pGenesil-2-shAURKA treatment.…”

Section: Discussionsupporting

confidence: 65%

A vector-based short hairpin RNA targeting Aurora A inhibits breast cancer growth

Wan

Huang²,

Yang³

et al. 2010

Int J Oncol

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Abstract. Aurora A plays an essential role in centrosome maturation, separation and in the formation of the mitotic bipolar spindle. Overexpression or amplication of Aurora A gene has been detected in many cancer cell lines and various tumor tissues, including breast cancer, suggesting that Aurora A might be drug target for breast cancer treatment. In the current study, short hairpin RNA targeting Aurora A was cloned into pGenesil-2 plasmid vector and then transfected into MDA-MB-435S and ZR-75-30 human breast cancer cells using cationic liposome. Reduced expression of Aurora A was detected by RT-PCR and Western blot. The effect of pGenesil-2-shAURKA plasmid on tumor growth in MDA-MB-435S xenogenic implantation model was studied. pGenesil-2-shAURKA plasmid inhibited tumor growth significantly by systemantic administration. To further study the underlying mechanisms, cell apoptosis and proliferation were investigated by flow cytometric analysis, propidium iodide staining, TUNEL and Ki-67 immunostaining respectively. Increased apoptosis and reduced cell proliferation were detected in vitro and in vivo studies. In summary, our results suggested that specific knockdown of Aurora A expression by vector based shRNA may be a potential therapy for human breast cancer. IntroductionBreast cancer is the most commonly diagnosed cancer in women worldwide. More than 1.15 million women were diagnosed with breast cancer in 2002 (1). Registry data showed that breast cancer incidence has been increasing since 1973, especially in low and middle-income countries.In China, urban registries showed 20-30% increase in the past decade (2). Current breast cancer incidence and mortality rates (~180,510 and 40,940 cases in 2007 in the United States, respectively) (3) highlight the need to explore alternative therapeutic strategies.The process of cell division is instrumental to the development and progression of tumors, and targeting cell division has been proved as a successful antitumor therapy. A number of trials has addressed the benefit of adding a taxane (paclitaxel or docetaxel) to an anthracycline-based adjuvant chemotherapy regimen in breast cancer (4,5), suggesting that the molecules involved in cell cycle and division may be targets for cancer treatment.Aurora A is an oncogenic serine/threonine kinase that plays an essential role in centrosome maturation, separation and in the formation of the mitotic bipolar spindle in various organisms (6-10). It has been reported that its ectopic expression in immortalized NIH/3T3 cells is sufficient to provoke their transformation, defining Aurora A as an oncogene (11). Overexpression or amplication of Aurora A gene has been detected in many cancer cell lines and various tumor tissues, including breast cancer (reviewed in ref. 12). Nadler et al reported that Aurora A expression defines a population of patients with decreased survival, whereas Aurora B expression does not, suggesting that Aurora A might be the preferred drug target in breast cancer (13).RNA interference is a specific way of g...

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Section: Discussionsupporting

confidence: 65%

A vector-based short hairpin RNA targeting Aurora A inhibits breast cancer growth

Wan

Huang²,

Yang³

et al. 2010

Int J Oncol

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“…Several studies including those in head and neck squamous carcinoma, ovarian cancer, neuroblastoma, and glioblastoma have shown that high levels of Aurora A kinase messenger RNA in tumor specimens correlate with centrosome abnormalities, tumor progression and shortened survival [41,50,51]. These findings support a role for Aurora kinases in oncogenesis.…”

Section: High Aurora a And B Expression Are Asso-ciated With Poor Promentioning

confidence: 77%

Targeting Aurora Kinases in Cancer Treatment

Kelly

Ecsedy

Mahalingam

et al. 2011

CDT

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The Aurora family of serine/threonine kinases is essential for chromosome alignment, segregation, centrosomal maturation, mitotic spindle formation, and cytokinesis during mitosis. Their fundamental role in cell cycle regulation and aberrant expression in a broad range of malignancies prompted the development of small molecules that selectively inhibit their activity. Recent studies have revealed new insights into the cellular effects of Aurora kinase inhibition. Moreover, early phase clinical studies have shown that these agents have therapeutic efficacy. In this review, we will outline the functions of Aurora kinases in normal cell division and in malignancy. We will focus on recent preclinical and clinical studies that have explored the mechanism of action and clinical effect of Aurora inhibitors in cancer treatment.

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“…[37][38][39][40] In addition, higher expression of Aurora A mRNA or protein is associated with poor survival of glioblastoma patients. [40][41][42] Expression of Aurora B protein is more common in patients with short survival times than in those with long survival times. 43 Therefore, several trials have attempted to use an Aurora kinase inhibitor to treat glioblastoma.…”

Section: Discussionmentioning

confidence: 99%

An Aurora kinase inhibitor, AMG900, inhibits glioblastoma cell proliferation by disrupting mitotic progression

et al. 2018

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The Aurora kinase family of serine/threonine protein kinases comprises Aurora A, B, and C and plays an important role in mitotic progression. Several inhibitors of Aurora kinase have been developed as anti‐cancer therapeutics. Here, we examined the effects of a pan‐Aurora kinase inhibitor, AMG900, against glioblastoma cells. AMG900 inhibited proliferation of A172, U‐87MG, and U‐118MG glioblastoma cells by upregulating p53 and p21 and subsequently inducing cell cycle arrest and senescence. Abnormal cell cycle progression was triggered by dysregulated mitosis. Mitosis was prolonged due to a defect in mitotic spindle assembly. Despite the presence of an unattached kinetochore, BubR1, a component of the spindle assembly checkpoint, was not recruited. In addition, Aurora B was not recruited to central spindle at anaphase. Abnormal mitotic progression resulted in accumulation of multinuclei and micronuclei, a type of chromosome missegregation, and ultimately inhibited cell survival. Therefore, the data suggest that AMG900‐mediated inhibition of Aurora kinase is a potential anti‐cancer therapy for glioblastoma.

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Comparative immunohistochemical analysis of aurora-A and aurora-B expression in human glioblastomas. Associations with proliferative activity and clinicopathological features

Cited by 23 publications

References 36 publications

A vector-based short hairpin RNA targeting Aurora A inhibits breast cancer growth

A vector-based short hairpin RNA targeting Aurora A inhibits breast cancer growth

Targeting Aurora Kinases in Cancer Treatment

An Aurora kinase inhibitor, AMG900, inhibits glioblastoma cell proliferation by disrupting mitotic progression

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