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      Phosphoglycerate mutase 1 is highly expressed in C6 glioma cells and human astrocytoma

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          Abstract

          The aim of the present study was to examine the expression of phosphoglycerate mutase 1 (PGAM1) in astrocytomas, and to investigate its role in the progression of astrocytomas. The expression of PGAM1 mRNA in rat C6 glioma cells and normal astrocytes was determined using the reverse transcription-semi-quantitative polymerase chain reaction, and immunohistochemistry was used to detect the expression of PGAM1 protein in human astrocytomas and adjacent brain tissue. These data suggested that the expression of PGAM1 in rat C6 glioma cells was significantly increased compared with that of normal astrocytes (P<0.05), and the expression of PGAM1 protein in human astrocytoma tissue was significantly increased compared with that of the brain tissue surrounding the tumor (P<0.05). In addition, PGAM1 protein was more frequently expressed in high-grade astrocytomas compared with low-grade astrocytomas. These data indicate that the expression of PGAM1 is increased in C6 cells and human astrocytomas, and PGAM1 is probably involved in the tumorigenesis and progression of glioma, which may be a potential target for glioma treatment.

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          Most cited references17

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          Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia.

          Cancer cells generally exhibit increased glycolysis for ATP generation (the Warburg effect) due in part to mitochondrial respiration injury and hypoxia, which are frequently associated with resistance to therapeutic agents. Here, we report that inhibition of glycolysis severely depletes ATP in cancer cells, especially in clones of cancer cells with mitochondrial respiration defects, and leads to rapid dephosphorylation of the glycolysis-apoptosis integrating molecule BAD at Ser(112), relocalization of BAX to mitochondria, and massive cell death. Importantly, inhibition of glycolysis effectively kills colon cancer cells and lymphoma cells in a hypoxic environment in which the cancer cells exhibit high glycolytic activity and decreased sensitivity to common anticancer agents. Depletion of ATP by glycolytic inhibition also potently induced apoptosis in multidrug-resistant cells, suggesting that deprivation of cellular energy supply may be an effective way to overcome multidrug resistance. Our study shows a promising therapeutic strategy to effectively kill cancer cells and overcome drug resistance. Because the Warburg effect and hypoxia are frequently seen in human cancers, these findings may have broad clinical implications.
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            Isolation and culture of mouse cortical astrocytes.

            Astrocytes are an abundant cell type in the mammalian brain, yet much remains to be learned about their molecular and functional characteristics. In vitro astrocyte cell culture systems can be used to study the biological functions of these glial cells in detail. This video protocol shows how to obtain pure astrocytes by isolation and culture of mixed cortical cells of mouse pups. The method is based on the absence of viable neurons and the separation of astrocytes, oligodendrocytes and microglia, the three main glial cell populations of the central nervous system, in culture. Representative images during the first days of culture demonstrate the presence of a mixed cell population and indicate the timepoint, when astrocytes become confluent and should be separated from microglia and oligodendrocytes. Moreover, we demonstrate purity and astrocytic morphology of cultured astrocytes using immunocytochemical stainings for well established and newly described astrocyte markers. This culture system can be easily used to obtain pure mouse astrocytes and astrocyte-conditioned medium for studying various aspects of astrocyte biology.
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              Perturbational profiling of a cell-line model of tumorigenesis by using metabolic measurements.

              Weinberg and coworkers have used serial transduction of a human, primary fibroblast cell line with the catalytic domain of human telomerase, large T antigen, small T antigen, and an oncogenic allele of H-ras to study stages leading toward a fully transformed cancerous state. We performed a three-dimensional screening experiment using 4 cell lines, 5 small-molecule perturbagens (2-deoxyglucose, oxamate, oligomycin, rapamycin, and wortmannin), and a large number of metabolic measurements. Hierarchical clustering was performed to obtain signatures of the 4 cell lines, 24 cell states, 5 perturbagens, and a number of metabolic parameters. Analysis of these signatures and sensitivities of the cell lines to the perturbagens provided insights into the bioenergetic states of progressively transformed cell lines, the effect of oncogenes on small-molecule sensitivity, and global physiological responses to modulators of aerobic and anaerobic metabolism. We have gained insight into the relationship between two models of carcinogenesis, one (the Warburg hypothesis) based on increased energy production by glycolysis in cancer cells in response to aberrant respiration, and one based on cancer-causing genes. Rather than being opposing models, the approach described here suggests that these two models are interlinked. The cancer-causing genes used in this study appear to increase progressively the cell's dependence on glycolytic energy production and to decrease its dependence on mitochondrial energy production. However, mitochondrial biogenesis appears to have a more complex dependence, increasing to its greatest extent at an intermediate degree of transduction rather than at the fully transformed state.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                June 2018
                12 April 2018
                12 April 2018
                : 15
                : 6
                : 8935-8940
                Affiliations
                [1 ]Department of Neurosurgery, Shandong Cancer Hospital, Shandong Provincial Institute of Cancer Prevention and Treatment, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250017, P.R. China
                [2 ]Department of Respiration Medicine, Xi'an Chest Hospital, Xi'an, Shanxi 710100, P.R. China
                [3 ]Department of Neurosurgery, Zhangqiu People's Hospital of Shandong Province, Jinan, Shandong 250200, P.R. China
                [4 ]Department of Radiology, Zhangqiu People's Hospital of Shandong Province, Jinan, Shandong 250200, P.R. China
                [5 ]Department of Chinese Acupuncture, Zhangqiu People's Hospital of Shandong Province, Jinan, Shandong 250200, P.R. China
                [6 ]Department of Pathology and Laboratory Medicine, North Shore University Hospital and Long Island Jewish Medical Center, Northwell Health, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Lake Success, NY 11042, USA
                [7 ]Department of Neurosurgery, Qilu Hospital of Shandong University, Brain Science Research Institute of Shandong University, Jinan, Shandong 250117, P.R. China
                [8 ]Department of Oncology, Shandong Cancer Hospital, Shandong Provincial Institute of Cancer Prevention and Treatment, Jinan, Shandong 250117, P.R. China
                Author notes
                Correspondence to: Professor Jin-Ming Yu, Department of Oncology, Shandong Cancer Hospital, Shandong Provincial Institute of Cancer Prevention and Treatment, 440 Yan Ji Road, Huaiyin, Jinan, Shandong 250117, P.R. China, E-mail: lzg05211@ 123456126.com
                Article
                OL-0-0-8477
                10.3892/ol.2018.8477
                5958715
                cc85bb02-83a3-4203-9fde-ec7437758bf3
                Copyright: © Liu et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 15 December 2015
                : 24 April 2017
                Categories
                Articles

                Oncology & Radiotherapy
                phosphoglycerate mutase l,glioma,astrocytoma,semi-quantitative reverse transcription polymerase chain reaction,immunohistochemistry

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