脂肪酸结合蛋白5和细胞维甲酸结合蛋白2在脑胶质瘤中的表达

Expression of Fatty Acid-binding Protein 5 and Cellular Retinoic Acid-binding Protein 2 in Gliomas

目的探讨脂肪酸结合蛋白5(fatty acid-binding protein 5,FABP5)与细胞维甲酸结合蛋白2(cellular retinoic acid-binding protein 2,CRABP2)在脑胶质瘤中的表达及与脑胶质瘤病理级别、维甲酸治疗抵抗的关系。方法应用免疫组织化学染色法检测125例脑星型细胞瘤组织中FABP5及CRABP2蛋白表达。全反式维甲酸作用前后,以Brdu-ELISA法检测胶质瘤细胞增殖,并以实时荧光定量PCR检测胶质瘤细胞株中FABP5及CRABP2在m RNA水平的表达。结果 FABP5阳性细胞比例在WHOⅡ级星型细胞瘤中占(16±9)%,Ⅲ级中占(33±22)%,Ⅳ级中占(50±29)%,FABP5蛋白表达与胶质瘤病理级别呈显著正相关(P<0.05)。CRABP2阳性细胞比例在Ⅱ级星型细胞瘤中占(46±12)%,WHOⅢ级中占(30±15)%,Ⅳ级中占(10±9)%,CRABP2蛋白表达与胶质瘤病理级别呈显著负相关(P<0.05)。全反式维甲酸促进了胶质瘤细胞株的增殖,全反式维甲酸作用后胶质瘤细胞FABP5 m RNA表达显著上调,而CRABP2显著下调。结论 FABP5及CRABP2的异常表达与胶质瘤恶性程度相关,并可能介导了胶质瘤细胞对维甲酸的分化抵抗效应。

Objective To investigate the correlation between the expression of fatty acid-binding protein 5(FABP5) cellular retinoic acid-binding protein 2(CRABP2) and WHO grades as well as the retinoic acid resistance of glioma. Methods Immunohistochemistry staining was applied to detect FABP5 and CRABP2 protein expression in 125 brain astrocytoma samples. Brdu-ELISA was applied to detect the proliferation and real-time quantitative fluorescence PCR was performed to detect m RNA expression of the two proteins in glioma cell lines before and after all-trans retinoic acid(ATRA) treatment. Results The percentage of FABP5 positive cells was(16±9)% in glioma samples of WHO grade Ⅱ,(33±22)% in WHO grade Ⅲ and(50±29)% in WHO grade Ⅳ; FABP5 expression was positively correlated with WHO grades of glioma(P<0.05). The percentage of CRABP2 positive cells was(46±12)% in glioma samples of WHO grade Ⅱ,(30±15)% in WHO grade Ⅲ and(10±9)% in WHO grade Ⅳ; CRABP2 expression was negatively correlated with WHO grades of glioma(P<0.05). ATRA promoted the proliferation of glioma cell lines. Moreover, after ATRA treatment, FABP5 m RNA expression was increased while CRABP2 m RNA expression was decreased significantly. Conclusion The abnormal expression of FABP5 and CRABP2 are closely associated with glioma grades and may play roles in the retinoic acid resistance of glioma.