Over-expression of LRIG1 suppresses biological function of pituitary adenoma via attenuation of PI3K/AKT and Ras/Raf/ERK pathways in vivo and in vitro
Over-expression of LRIG1 suppresses biological function of pituitary adenoma via attenuation of PI3K/AKT and Ras/Raf/ERK pathways in vivo and in vitro
复制标题
LRIG1 的过表达通过体内和体外减弱 PI3K/AKT 和 Ras/Raf/ERK 通路抑制垂体腺瘤的生物学功能。
DOI：
10.1007/s11596-016-1625-4
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发表时间：
2016-08-01
影响因子：
--
通讯作者：
Zhang, Yan
中科院分区：
文献类型：
--
作者：
Cheng, Shi-qi;Fan, Heng-yi;Zhang, Yan
垂体腺瘤是一种常见的颅内良性肿瘤，目前的治疗方法对部分垂体腺瘤难以治愈。ErbB受体家族信号通路调节PAs激活相关基因的表达。抑制表皮生长因子受体（EGFR）可以抑制PA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（Leucine-rich repeats and immunoglobulin-like domains protein 1，LRIG 1）是ErbB受体家族的负性介导基因，在多种肿瘤中发挥作用。然而，关于LRIG 1在肺动脉瘤中的功能作用的研究却很少。本研究旨在探讨LRIG 1在肺动脉高压中的潜在作用及其调控机制。首先，我们研究了LRIG 1在细胞迁移、转染LRIG 1或对照的PA侵袭中的作用。探讨其在体内对肺动脉瘤细胞增殖和凋亡的影响。为研究LRIG 1的调控机制，我们采用体外Western blotting和体内外RT-PCR方法检测了PI 3 K/AKT和Ras/Raf/ERK信号通路分子因子的表达。在体内和体外实验中发现LRIG 1过表达抑制了肺动脉瘤细胞的迁移、侵袭和增殖，并促进了肺动脉瘤细胞的凋亡。此外，LRIG 1还能抑制PA中PI 3 K/AKT和Ras/Raf/ERK信号通路的表达。LRIG 1作为一种负性介导的肿瘤基因，通过抑制PI 3 K/AKT和Ras/Raf/ERK信号通路抑制PAs的生物学功能，有望成为PAs基因治疗的新靶点。
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.