Department of Neuropathology, Derriford Hospital, UK.
Histopathology. 2009 Dec;55(6):744-9. doi: 10.1111/j.1365-2559.2009.03440.x.
Schwannomas are common tumours that may be multiple in neurofibromatosis type 2, when they may be difficult to treat without significant morbidity using surgery and radiosurgery. Previous in vitro work has suggested that merlin loss is associated with activation of the JNK/JUN, PI3K/AKT and MEK/ERK pathways and that these pathways may be susceptible to pharmacological inhibition. The aim was to investigate the expression of proteins involved in these pathways in human schwannomas in situ.
Immunohistochemistry using antibodies to AKT, pAKT, MEK, pMEK, ERK, pERK, JUN and pJUN was applied to 16 schwannomas (sporadic and NF2), and the results were compared with those seen in traumatic neuromas. Increased expression of pMEK, pERK and pJUN was seen in the schwannomas samples and of pAKT in schwannomas and controls.
These findings provide further direct evidence for activation of the JNK/JUN, PI3K/AKT and MEK/ERK signalling pathways in schwannomas and support the development of therapeutic agents directed against these pathways for the treatment of this group of tumours.
神经鞘瘤是一种常见的肿瘤，在神经纤维瘤病 2 型中可能是多发性的，在不进行手术和放射外科治疗的情况下，这些肿瘤可能会导致严重的发病率。先前的体外研究表明，神经鞘瘤蛋白（merlin）缺失与 JNK/JUN、PI3K/AKT 和 MEK/ERK 通路的激活有关，这些通路可能容易受到药物抑制。本研究旨在研究这些通路相关蛋白在人神经鞘瘤中的表达情况。
采用 AKT、pAKT、MEK、pMEK、ERK、pERK、JUN 和 pJUN 抗体的免疫组织化学方法，对 16 例神经鞘瘤（散发性和 NF2 型）进行了检测，并将结果与创伤性神经瘤进行了比较。在神经鞘瘤样本中观察到 pMEK、pERK 和 pJUN 的表达增加，在神经鞘瘤和对照组中观察到 pAKT 的表达增加。
这些发现为神经鞘瘤中 JNK/JUN、PI3K/AKT 和 MEK/ERK 信号通路的激活提供了进一步的直接证据，并支持开发针对这些通路的治疗药物，以治疗这组肿瘤。
