%0 Journal Article
%T Overexpression of S6 Kinase 1 in Brain Tumours Is Associated with Induction of Hypoxia-Responsive Genes and Predicts Patients' Survival
%A Heba M.S. Ismail
%J Journal of Oncology
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/416927
%X mTOR/S6K pathway is a crucial regulator of cell growth and metabolism. Deregulated signalling via S6K has been linked to various human pathologies, including metabolic disorders and cancer. Many of the molecules signalling upstream of S6K have been shown to be either mutated or overexpressed in tumours, leading to S6K activation. The role of S6K1 in brain tumours is not fully investigated. In this study, we investigated the gene expression profile of S6 kinases in brain and CNS tumours using the publically available Cancer Microarray Database. We found that S6K1 but not S6K2 gene is overexpressed in brain tumours and this upregulation is associated with patients¡¯ poor survival. Furthermore, we interrogated Oncomine database for the expression profile of hypoxia-induced genes using a literature-defined concept. This gene list included HIF1A, VEGFA, SOX4, SOX9, MMP2, and NEDD9. We show that those genes are upregulated in all brain tumour studies investigated. Additionally, we analysed the coexpression profile of S6K1 and hypoxia responsive genes. The analysis was done across 4 different brain studies and showed that S6K1 is co-overexpressed with several hypoxia responsive genes. This study highlights the possible role of S6K1 in brain tumour progression and prediction of patients¡¯ survival. However, new epidemiological studies should be conducted in order to confirm these associations and to refine the role of S6K1 in brain tumours as a useful marker for patients¡¯ survival. 1. Introduction Brain and other central nervous system (CNS) cancers include a variety of histopathologic subtypes, but the most common, by far, are gliomas. These tumours, which arise from the glial cells that surround and support neurons, include astrocytoma, glioblastoma, oligodendroglioma, oligoastrocytoma, and ependymoma. Medulloblastoma, another neuroepithelial cancer, is relatively common in children but rare in adults. Brain cancers in children typically arise in the cerebellum, whereas brain cancers in adults are more likely to occur in the cerebral hemispheres [1]. In adults, older age at diagnosis of brain cancer is associated with higher tumour grade and poorer prognosis. Indeed, glioblastoma is among the most lethal of all cancers. Brain and central nervous system (CNS) tumours occur at each stage of life and are therefore classified as embryonic, paediatric, and adult cancers [2, 3]. According to Central Brain Tumour Registry of the Unites States (CBTRUS), the prevalence rate for all primary brain and central nervous system tumours was estimated to be 209.0 per 100,000 in
%U http://www.hindawi.com/journals/jo/2012/416927/