Carroll R S, Black P M, Zhang J, Kirsch M, Percec I, Lau N, Guha A
Neurosurgical Laboratories and Brain Tumor Center, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
J Neurosurg. 1997 Aug;87(2):315-23. doi: 10.3171/jns.1997.87.2.0315.
Previous studies have demonstrated expression of epidermal growth factor receptors (EGFRs) in human cerebral meningiomas. However, the activation status of the EGFRs and whether they activate cytoplasmic mitogenic signaling pathways are not known. In this study, using Northern blot analysis and the polymerase chain reaction, the authors report expression of epidermal growth factor, transforming growth factor-alpha, and EGFR messenger RNA in 27 meningioma specimens. Using Western blot and immunohistochemical analyses of the meningioma samples, the authors demonstrate that the EGFRs expressed by these meningiomas are activated. These activated EGFRs interact with and phosphorylate Shc, an SH2 domain-containing adapter protein that is important in transducing mitogenic signals from EGFRs to the nucleus via activation of the Ras signaling pathway. These results support the concept that activation of EGFRs in human meningiomas by autocrine/paracrine stimulation may contribute to their proliferation.
以往的研究已证实在人脑膜瘤中存在表皮生长因子受体（EGFRs）的表达。然而，EGFRs的激活状态以及它们是否激活细胞质有丝分裂信号通路尚不清楚。在本研究中，作者运用Northern印迹分析和聚合酶链反应，报告了在27个脑膜瘤标本中表皮生长因子、转化生长因子-α和EGFR信使核糖核酸的表达情况。通过对脑膜瘤样本进行蛋白质印迹和免疫组织化学分析，作者证明这些脑膜瘤所表达的EGFRs被激活。这些被激活的EGFRs与含SH2结构域的衔接蛋白Shc相互作用并使其磷酸化，Shc在通过激活Ras信号通路将有丝分裂信号从EGFRs转导至细胞核的过程中起重要作用。这些结果支持这样一种观点，即自分泌/旁分泌刺激激活人脑膜瘤中的EGFRs可能有助于其增殖。
