Expression of astrocyte elevated gene-1 (AEG-1) in human meningiomas and its roles in cell proliferation and survival

• Published in: Journal of neuro-oncology 2015-01, Vol.121 (1), p.31-39
• Main Authors: Park, Kyung-Jae, Yu, Mi Ok, Song, Na-Hyun, Kong, Doo-Sik, Park, Dong-Hyuk, Chae, Yang-Seok, Chung, Yong-Gu, Kang, Shin-Hyuk
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - physiology; Carcinogenesis; Cell Adhesion Molecules - antagonists & inhibitors; Cell Adhesion Molecules - metabolism; Cell Line, Tumor; Cell Proliferation - physiology; Cell Survival - physiology; Humans; Laboratory Investigation; Medicine; Medicine & Public Health; Meningioma - pathology; Meningioma - physiopathology; Mice, Nude; Neoplasm Grading; Neoplasm Transplantation; Neurology; Oncology; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; RNA, Messenger - metabolism
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-014-1603-2

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.