Expression and activation of epidermal growth factor receptors in meningiomas

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Abstract
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.