Ferrer-Font Laura, Alcaraz Estefania, Plana Maria, Candiota Ana Paula, Itarte Emilio, Arús Carles
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.
Pathol Oncol Res. 2016 Jul;22(3):633-7. doi: 10.1007/s12253-015-9987-7. Epub 2015 Oct 14.
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.
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。