Cheng Shi-Qi, Fan Heng-Yi, Xu Xin, Gao Wei-Wei, Lv Shi-Gang, Ye Min-Hua, Wu Miao-Jing, Shen Xiao-Li, Cheng Zu-Jue, Zhu Xin-Gen, Zhang Yan
Department of Neurosurgery, the Second Affiliated Hospital, Nanchang University, Nanchang, 330006, China.
Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China.
J Huazhong Univ Sci Technolog Med Sci. 2016 Aug;36(4):558-563. doi: 10.1007/s11596-016-1625-4. Epub 2016 Jul 28.
Pituitary adenomas (PAs) are well known as a common intracranial benign tumor, and a portion of PAs are refractory to current therapeutic methods. ErbB receptors family signaling pathway regulates the expression of PAs activation associated gene. Inhibition of epidermal growth factor receptor (EGFR) can inhibit proliferation of PAs. Leucine-rich repeats and immunoglobulin-like domains protein 1 ( LRIG1), a negative mediated gene of ErbB receptors family, plays a role in many tumors. However, there are seldom researches about the functional role of LRIG1 in PAs. The aim of this study is to explore the potential effect of LRIG1 and its regulating mechanism in PAs. First, we investigated the role of LRIG1 in cell migration, invasion of PAs with transfected LRIG1 or control. Then, we explored its impact on cell proliferation and apoptosis of PAs in vivo. To study the regulating mechanism of LRIG1, we examined the expression of molecular factor of PI3K/AKT and Ras/Raf/ERK pathway using Western blotting in vitro and RT-PCR in vitro and in vivo. It was found that LRIG1 over-expression inhibited cell migration, invasion and proliferation, and promoted apoptosis of PAs in vivo and in vitro. Furthermore, LRIG1 suppressed the expression of signaling of PI3K/AKT and Ras/Raf/ERK pathways in PAs. LRIG1, as a negative mediated gene of tumor, can inhibit biological function of PAs via inhibiting PI3K/AKT and Ras/Raf/ERK pathways, and it might be a new target for gene therapy of PAs.
垂体腺瘤（PAs）是一种常见的颅内良性肿瘤，目前已知一部分垂体腺瘤对现有治疗方法具有耐药性。表皮生长因子受体（ErbB）家族信号通路调节垂体腺瘤激活相关基因的表达。抑制表皮生长因子受体（EGFR）可抑制垂体腺瘤的增殖。富含亮氨酸重复序列和免疫球蛋白样结构域蛋白1（LRIG1）是ErbB受体家族的负调控基因，在多种肿瘤中发挥作用。然而，关于LRIG1在垂体腺瘤中的功能作用的研究很少。本研究旨在探讨LRIG1在垂体腺瘤中的潜在作用及其调控机制。首先，我们通过转染LRIG1或对照来研究LRIG1在垂体腺瘤细胞迁移和侵袭中的作用。然后，我们在体内探索其对垂体腺瘤细胞增殖和凋亡的影响。为了研究LRIG1的调控机制，我们使用蛋白质免疫印迹法在体外以及实时荧光定量聚合酶链反应（RT-PCR）在体外和体内检测PI3K/AKT和Ras/Raf/ERK信号通路分子因子的表达。结果发现，LRIG1过表达在体内和体外均抑制垂体腺瘤细胞的迁移、侵袭和增殖，并促进其凋亡。此外，LRIG1抑制垂体腺瘤中PI3K/AKT和Ras/Raf/ERK信号通路的表达。LRIG1作为一种肿瘤负调控基因，可通过抑制PI3K/AKT和Ras/Raf/ERK信号通路来抑制垂体腺瘤的生物学功能，可能是垂体腺瘤基因治疗的新靶点。
