胶质瘤中MKK7与c-Jun磷酸化的表达及其相关性

Expression of MKK7 and Phospho-c-Jun in Glioma and Their Correlation

目的探讨胶质瘤中MKK7和c-Jun磷酸化(p-c-Jun)的表达及意义,分析两者表达的相关性。方法选取弥漫型星形细胞瘤(15例)、少突胶质细胞瘤(5例)、间变性星形细胞瘤(11例)、间变性少突胶质细胞瘤(8例)、胶质母细胞瘤(53例)及其瘤旁正常脑组织(25例)共117例,采用免疫组织化学法检测MKK7、c-Jun及p-c-Jun的表达。体外培养神经胶质瘤细胞株U87,用脂质体转染MKK4-siRNA、MKK7-siRNA和对照siRNA,48h后Westernblot检测MKK7、c-Jun及p-c-Jun的表达水平。结果胶质母细胞瘤中p-c-Jun及MKK7的表达均明显高于其他组织学类型胶质瘤及胶质母细胞瘤瘤旁正常脑组织中的表达(P=0.000,P=0.000)。随着胶质瘤WHO分级的升高,p-c-Jun及MKK7的表达增高,且与WHO分级呈明显正相关(r=0.494,P=0.000;r=0.606,P=0.000)。胶质瘤及胶质母细胞瘤瘤旁正常脑组织中MKK7与p-c-Jun的表达存在正相关关系(r=0.387,P=0.000)。沉默神经胶质瘤细胞株U87MKK7表达抑制了c-Jun磷酸化水平。结论MKK7可以通过调控JNK/c-Jun活性进而促进胶质母细胞瘤的发生。

Objective To investigate the expression of phospho-c-Jun and MKK7 in gliomas and their correlation. Methods We collected and analyzed retrospectively 92 cases of gliomas, including 15 cases of diffuse astrocytoma, 5 cases of oligodendroglioma, 11 cases of anaplastic astrocytoma, 8 cases of anaplastic oligodendroglioma 53 cases of glioblastoma and 25 normal brain tissues adjacent to glioblastoma. The expression of c-Jun, phospho-c-Jun and MKK7 were detected by immunohistochemical staining. Glioma U87 cell line cultured in vitro was transfected with MKK4-siRNA, MKK7-siRNA and control siRNA for 48h, respectively. Western blot was performed to test the expression of c-Jun, phospho-c-Jun and MKK7. Results The expression of p-c-Jun and MKK7 in glioblastoma were significantly higher than those in other glioma and normal brain tissues adjacent to glioblastomas(P=0.000, P=0.000). The expression of MKK7 and phospho-c-Jun were positively correlated with WHO grading of gliomas (r=0.494, P=0.000;r=0.606, P=0.000). There was positive correlation between the expression of MKK7 and p-c-Jun (r=0.387, P=0.000). The knockdown of MKK7 suppressed c-Jun activities. Conclusion MKK7 promotes the development of glioblastoma by regulating the activity of c-Jun.