14-3-3蛋白在人脑胶质瘤中的表达及生物学意义

目的检测14-3-3蛋白在人脑胶质瘤中的表达情况,探讨其在胶质瘤发生发展中的生物学意义。方法采用免疫组化亲和素-生物素过氧化物酶复合物(ABC)法检测5个胶质瘤细胞系(U251MG,U87MG,BT325,SHG44和C6)、121例人脑胶质瘤石蜡标本和10例正常脑组织中14-3-3蛋白的表达情况。分析14-3-3蛋白的表达在胶质瘤发生发展中的作用。结果在正常脑组织标本中,13-3-3蛋白主要表达于神经元的胞体和突起,仅在少数的胶质细胞中可见14-3-3蛋白的弱表达。然而,5个胶质瘤细胞系和绝大部分星形细胞瘤中可见14-3-3蛋白的阳性表达,其表达阳性率为:Ⅰ级78.6%(11/14),II级75%(18/24),III级76.2%(16/21),IV级80%(20/25)。不同恶性级别的星形细胞瘤中,14-3-3蛋白的阳性表达率无显著差别,但14-3-3蛋白的表达强度和范围有随肿瘤的恶性度增高而增加的趋势。其它类型的胶质瘤中也可见14-3-3蛋白的大量表达,其表达阳性率为:少突胶质细胞瘤66.7%(4/6),间变型少突胶质细胞瘤100%(4/4),室管膜瘤50%(2/4),间变型室管膜瘤66.7%(2/3),脉络从乳头状瘤100%(5/5),松果体细胞瘤100%(3/3),髓母细胞瘤66.7%(8/12)。结论14-3-3蛋白在人脑胶质瘤中有大量的表达。14-3-3蛋白表达上调可能是胶质瘤细胞对抗调亡的一种共同机制,以14-3-3蛋白为靶点有望成为一种有前景的新的胶质瘤生物学治疗方法。

Expression and biological significance of 14-3-3 in gliomas

Objective To investigate the expression and its biological significance of 14-3-3 proteins in human gliomas. Methods The expression of 14-3-3 proteins was detected in five glioma cell lines (U251MG, U87MG,BT325, SHG44, and C6), 121 cases of formalin-fixed, paraffin embedded archival tumor tissue from patients with glioma, and 10 normal human brain tissues by immunohistochemical avidin-biotin-peroxidase complex (ABC) method. And the biological significance of 14-3-3 proteins expression was analyzed in the etiopathogenesis of glioma.Results In the normal control brains, 14-3-3 immunoreactivity was localized mainly in the neuronal somata and processes, and some glial cells showed only weak immunoreactivity. However, 14-3-3 immunoreactivity was seen in all of the five glioma cell lines and the majority of astrocytomas [78.6% in grade Ⅰ (11/14), 75% in grade Ⅱ (18/24), 76.2% in grade Ⅲ (16/21), and 80% in grade Ⅳ (20/25)]. No differences were found among the positive expression rates of 14-3-3 in different grades of astrocytomas. But the intensity and the degree of 14-3-3 expression showed trends with tumor grade. The 14-3-3 immunoreactivity was also seen in the majority of other gliomas [66.7% in oligodendroglioma (4/6), 100% in anaplastic oligodendroglioma (4/4), 50% in ependymoma (2/4), 66.7% in anaplastic ependymoma (2/3), 100% in choroid plexus papilloma (5/5), 100% in pineocytoma (3/3), and 66.7% in medulloblastoma (8/12) ]. Conclusion Most human gliomas are positive for 14-3-3 proteins in this research. For most human gliomas, one common mechanism for escaping apoptosis may be the up-regulated expression of 14-3-3,and targeting 14-3-3 may be a novel promising strategy for the treatment of gliomas.