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GL261小鼠胶质母细胞瘤中的蛋白激酶CK2含量

Protein Kinase CK2 Content in GL261 Mouse Glioblastoma.

作者信息

Ferrer-Font Laura, Alcaraz Estefania, Plana Maria, Candiota Ana Paula, Itarte Emilio, Arús Carles

机构信息

Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica de Biociències, Edifici Cs, Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Spain.

Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Cerdanyola del Vallès, Spain.

出版信息

Pathol Oncol Res. 2016 Jul;22(3):633-7. doi: 10.1007/s12253-015-9987-7. Epub 2015 Oct 14.

DOI:10.1007/s12253-015-9987-7
PMID:26466942
Abstract

Glioblastoma (GBM) is the most prevalent and aggressive human glial tumour with a median survival of 14-15 months. Temozolomide (TMZ) is the standard chemotherapeutic choice for GBM treatment. Unfortunately, chemoresistence always ensues with concomitant tumour regrowth. Protein kinase CK2 (CK2) contributes to tumour development, proliferation, and suppression of apoptosis in cancer and it is overexpressed in human GBM. Targeting CK2 in GBM treatment may benefit patients. With this translational perspective in mind, we have studied the CK2 expression level by Western blot analysis in a preclinical model of GBM: GL261 cells growing orthotopically in C57BL/6 mice. The expression level of the CK2 catalytic subunit (CK2α) was higher in tumour (about 4-fold) and in contralateral brain parenchyma (more than 2-fold) than in normal brain parenchyma (p < 0.05). In contrast, no significant changes were found in CK2 regulatory subunit (CK2β) expression, suggesting an increased unbalance of CK2α/CK2β in GL261 tumours with respect to normal brain parenchyma, in agreement with a differential role of these two subunits in tumours.

摘要

胶质母细胞瘤(GBM)是最常见且侵袭性最强的人类胶质肿瘤,中位生存期为14 - 15个月。替莫唑胺(TMZ)是GBM治疗的标准化疗选择。不幸的是,化疗耐药总会伴随肿瘤复发。蛋白激酶CK2(CK2)在肿瘤的发生、发展、增殖以及细胞凋亡抑制中发挥作用,并且在人类GBM中过表达。在GBM治疗中靶向CK2可能使患者受益。基于这一转化医学观点,我们通过蛋白质印迹分析在GBM的临床前模型:C57BL/6小鼠原位生长的GL261细胞中研究了CK2的表达水平。CK2催化亚基(CK2α)在肿瘤中的表达水平(约4倍)以及在对侧脑实质中的表达水平(超过2倍)高于正常脑实质(p < 0.05)。相比之下,未发现CK2调节亚基(CK2β)表达有显著变化,这表明与正常脑实质相比,GL261肿瘤中CK2α/CK2β的失衡增加,这与这两个亚基在肿瘤中的不同作用一致。

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引用本文的文献

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Stem Cell-Like Properties of CK2β-down Regulated Mammary Cells.CK2β下调的乳腺细胞的干细胞样特性
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Targeting Protein Kinase CK2: Evaluating CX-4945 Potential for GL261 Glioblastoma Therapy in Immunocompetent Mice.

本文引用的文献

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Casein Kinase 2: a novel player in glioblastoma therapy and cancer stem cells.酪蛋白激酶2:胶质母细胞瘤治疗和癌症干细胞中的新角色。
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靶向蛋白激酶CK2:评估CX-4945在免疫健全小鼠中治疗GL261胶质母细胞瘤的潜力。
Pharmaceuticals (Basel). 2017 Feb 12;10(1):24. doi: 10.3390/ph10010024.
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细胞通透的蛋白激酶 CK2 和 PIM-1 的双重抑制剂:结构特征和药理学潜力。
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The role of protein kinase CK2 in glioblastoma development.蛋白激酶 CK2 在胶质母细胞瘤发展中的作用。
Clin Cancer Res. 2013 Dec 1;19(23):6335-7. doi: 10.1158/1078-0432.CCR-13-2478. Epub 2013 Oct 28.
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Targeting protein kinase CK2 suppresses prosurvival signaling pathways and growth of glioblastoma.靶向蛋白激酶 CK2 抑制胶质母细胞瘤的生存信号通路和生长。
Clin Cancer Res. 2013 Dec 1;19(23):6484-94. doi: 10.1158/1078-0432.CCR-13-0265. Epub 2013 Sep 13.
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CK2 inhibitor CX-4945 blocks TGF-β1-induced epithelial-to-mesenchymal transition in A549 human lung adenocarcinoma cells.CK2 抑制剂 CX-4945 阻断 TGF-β1 诱导的 A549 人肺腺癌细胞上皮间质转化。
PLoS One. 2013 Sep 4;8(9):e74342. doi: 10.1371/journal.pone.0074342. eCollection 2013.
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