American Association for Cancer Research
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Supplementary Table 1 from Aurora A is a negative prognostic factor and a new therapeutic target in human neuroblastoma

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posted on 2023-03-31, 23:30 authored by Xiaoying Shang, Susan M. Burlingame, M. Fatih Okcu, Ningling Ge, Heidi V. Russell, Rachel A. Egler, Rodney D. David, Sanjeev A. Vasudevan, Jianhua Yang, Jed G. Nuchtern
Supplementary Table 1 from Aurora A is a negative prognostic factor and a new therapeutic target in human neuroblastoma



We studied expression of the Aurora A gene and its clinical significance in a cohort of neuroblastoma patients. In addition, we investigated the antitumor activity of MLN8054, a novel small-molecule inhibitor of Aurora A kinase, on cultured NB cell lines in vitro. Aurora A mRNA expression was assessed by quantitative real-time PCR in tumor tissue specimens from 67 patients at diagnosis and in 9 human neuroblastoma cell lines. Western blot assays for Aurora A protein were done on tumor tissue of 53 patients. The results were correlated with various prognostic factors of neuroblastoma. Aurora A mRNA and protein expression were identified in 9 of 9 neuroblastoma cell lines. Overexpression of Aurora A mRNA in neuroblastoma tumor tissue is associated with high risk (P = 0.019), high-stage (International Neuroblastoma Staging System III and IV) tumors (P = 0.007), unfavorable histology (P = 0.007), MYCN amplification (P = 0.017), disease relapse (P = 0.019), and decreased progression-free survival (P < 0.0001) but not correlated with the age at diagnosis (P = 0.877). Similarly, Aurora A protein expression also significantly correlated with high risk (P = 0.011), high stage (P = 0.0028), unfavorable histology (P = 0.0006), MYCN amplification (P = 0.0029), and disease relapse (P = 0.044). Small interfering RNA–mediated knockdown of the endogenous Aurora A gene causes a proliferation defect and enhances chemosensitivity in human neuroblastoma cell lines. In support of these observations, the Aurora A kinase inhibitor, MLN8054, markedly inhibited growth of cultured neuroblastoma cell lines through an apoptosis-dependent pathway. Overexpression of Aurora A is associated with disease progression in neuroblastoma. Inhibition of this kinase is a promising modality for neuroblastoma treatment. [Mol Cancer Ther 2009;8(8):2461–9]

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