title: Expression of astrocyte elevated gene-1 (AEG-1) in human meningiomas and its roles in cell proliferation and survival.
abstract: Astrocyte elevated gene-1 (AEG-1) has recently been proposed to be involved in tumor development, invasion, and metastasis in several human cancers. However, the functional importance of AEG-1 expression in human meningioma has not been determined. We investigate the level of AEG-1 expression by quantitative reverse transcription PCR, immunohistochemistry analysis, and western blotting in various human meningioma tissues and cells. To determine the suppressive effect of AEG-1 on meningioma progression, we inhibited AEG-1 expression using small interfering RNA and examined cell proliferation, apoptosis, colony formation and tumorigenicity in a mouse xenograft model. AEG-1 expression was frequently elevated at both mRNA and protein levels in meningioma tumor tissues and in meningioma-derived cells as well. This elevation was more commonly observed in high-grade tumors than in benign ones. The knockdown of AEG-1 led to a decrease in overall cell proliferation, as well as anchorage-independent growth of malignant meningioma. In addition, apoptotic cell death occurred in AEG-1 depleted meningioma cells through p-Akt and Bcl-2 suppression. Furthermore, a mouse xenograft meningioma model showed that inhibition of AEG-1 expression significantly decreased tumor growth. Altogether, these data show that the elevation of AEG-1 contributes to the malignant progression of meningiomas, suggesting that AEG-1 could be a novel therapeutic target against human meningiomas.
authors.affiliation: Department of Neurosurgery, Korea University Medical Center, College of Medicine, Korea University, #126, 5-ga, Anam-Dong, Seongbuk-Gu, Seoul, 136-705, Korea.
authors.forename: Kyung-Jae
authors.initials: KJ
authors.lastname: Park
authors.forename: Mi Ok
authors.initials: MO
authors.lastname: Yu
authors.forename: Na-Hyun
authors.initials: NH
authors.lastname: Song
authors.forename: Doo-Sik
authors.initials: DS
authors.lastname: Kong
authors.forename: Dong-Hyuk
authors.initials: DH
authors.lastname: Park
authors.forename: Yang-Seok
authors.initials: YS
authors.lastname: Chae
authors.forename: Yong-Gu
authors.initials: YG
authors.lastname: Chung
authors.forename: Shin-Hyuk
authors.initials: SH
authors.lastname: Kang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D063646:Carcinogenesis; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins; D008579:Meningioma / Q000473:pathology / Q000503:physiopathology*; D008819:Mice, Nude; D060787:Neoplasm Grading; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins
chemical_list: C000595707:BCL2 protein, human; D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051057:Proto-Oncogene Proteins c-akt