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

J Neurooncol. 2015 Jan;121(1):31-9. doi: 10.1007/s11060-014-1603-2. Epub 2014 Sep 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Carcinogenesis
  • Cell Adhesion Molecules / antagonists & inhibitors
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / physiology*
  • Cell Survival / physiology*
  • Humans
  • Membrane Proteins
  • Meningioma / pathology
  • Meningioma / physiopathology*
  • Mice, Nude
  • Neoplasm Grading
  • Neoplasm Transplantation
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins

Substances

  • BCL2 protein, human
  • Cell Adhesion Molecules
  • MTDH protein, human
  • Membrane Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • RNA-Binding Proteins
  • Proto-Oncogene Proteins c-akt