Expression of Fatty Acid-binding Protein 5 and Cellular Retinoic Acid-binding Protein 2 in Gliomas
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摘要: 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mRNA水平的表达。结果 FABP5阳性细胞比例在WHO Ⅱ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）%，WHO Ⅲ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 mRNA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。
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关键词:
- 脂肪酸结合蛋白5 /
- 细胞维甲酸结合蛋白2 /
- 脑胶质瘤
Abstract: 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 mRNA 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 mRNA expression was increased while CRABP2 mRNA 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. -
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[1] Omuro A, DeAngelis LM. Glioblastoma and other malignant gliomas: a clinical review[J]. JAMA, 2013, 310(17): 1842-50. [2] Binello E, Germano IM. Targeting glioma stem cells: a novel framework for brain tumors[J]. Cancer Sci, 2011, 102(11): 19 58-66. [3] Puduvalli VK, Yung W K, Hess K R, et al. North American Brain Tumour Consortium.Phase Ⅱ study of fenretinide (NSC 374551) in adults with recurrent malignant gliomas: A North American Brain Tumour Consortium study[J]. J Clin Oncol, 2004, 22(21): 42 82-9. [4] Schug TT, Berry DC, Shaw NS, et al. Opposing effects of retinoic acid on cell growth result from alternate activation of two different nuclear receptors[J]. Cell, 2007, 129(4): 723-33. [5] Jeong CY1, Hah YS, Cho BI, et al. Fatty acid-binding protein 5 promotes cell proliferation and invasion in human intrahepatic cholangiocarcinoma[J].Oncol Rep, 2012, 28(4): 1283-92. [6] Liu RZ,Graham K,Glubrecht DD, et al.Association of FABP5 expression with poor survival in triple-negative breast cancer: implication for retinoic acid therapy[J]. Am J Pathol, 2011, 17 8(3): 997-1008. [7] Schug TT, Berry DC, Toshkov IA, et al. Overcoming retinoic acid-resistance of mammary carcinomas by diverting retinoic acid from PPARbeta/delta to RAR[J]. Proc Natl Acad Sci U S A, 2008, 10 5(21): 7546-51. [8] Gupta S, Pramanik D, Mukherjee R, et al. Molecular determinants of retinoic acid sensitivity in pancreatic cancer[J]. Clin Cancer Res, 2012, 18(1): 280-9. [9] Shi Z, Lou M, Zhao Y, et al. Effect of all-trans retinoic acid on the differentiation of U87 glioma stem/progenitor cells[J]. Cell Mol Neurobiol, 2013, 33(7): 943-51. [10] Li J, Zhang L, Fei Z, et al. Expression of Bcl-2 and Caspase-3 in apoptosis induced by all-trans-retinoic acid of C6 glioma cells in rat[J]. Zhonghua Shen Jing Wai Ke Ji Bing Yan Jiu Za Zhi, 2010, 9( 1): 23-6. [李娟, 张磊, 费舟, 等. ATRA诱导胶质瘤C6细胞凋亡 过程中Bcl-2和Caspase-3表达的研究[J].中华神经外科疾病研 究杂志, 2010, 9(1): 23-6.] [11] Jov?evska I, Ko?evar N, Komel R. Glioma and glioblastoma - how much do we (not) know? [J]. Mol Clin Oncol, 2013, 1(6): 93 5-41.
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