title: 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.
abstract: 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.
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital, Nanchang University, Nanchang, 330006, China.
authors.forename: Shi-Qi
authors.initials: SQ
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital, Nanchang University, Nanchang, 330006, China.
authors.forename: Heng-Yi
authors.initials: HY
authors.lastname: Fan
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital, Nanchang University, Nanchang, 330006, China.
authors.forename: Shi-Gang
authors.initials: SG
authors.lastname: Lv
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital, Nanchang University, Nanchang, 330006, China.
authors.forename: Min-Hua
authors.initials: MH
authors.lastname: Ye
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital, Nanchang University, Nanchang, 330006, China.
authors.forename: Miao-Jing
authors.initials: MJ
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital, Nanchang University, Nanchang, 330006, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Shen
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital, Nanchang University, Nanchang, 330006, China.
authors.forename: Zu-Jue
authors.initials: ZJ
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital, Nanchang University, Nanchang, 330006, China. zhuxingen2008@163.com.
authors.forename: Xin-Gen
authors.initials: XG
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital, Nanchang University, Nanchang, 330006, China. doctorzhangyan@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D051058:Oncogene Protein v-akt / Q000096:biosynthesis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D048490:raf Kinases / Q000096:biosynthesis / Q000235:genetics
chemical_list: C484445:LRIG1 protein, human; D008562:Membrane Glycoproteins; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D048490:raf Kinases
keywords: LRIG1; biological function; pituitary adenoma