Role of HER-2 activity in the regulation of malignant meningioma cell proliferation and motility.

Abstract

Meningiomas are common types of intracranial tumor. Invasive and malignant meningiomas present a significant therapeutic challenge due to high rates of recurrence and invasion. Understanding the molecular mechanism of invasion may assist in designing novel therapeutic approaches and improving patient survival rates. The HER‑2 gene has been demonstrated to be a useful predictor of tumor aggression, which promotes the survival and growth of cancer cells through the mitogen‑activated protein kinase and/or phosphatidylinositol 3‑kinase (PI3K)/AKT pathway. Until now, few studies have investigated the associateion between meningiomas and the expression of HER‑2, and the significance of HER‑2 in meningiomas remains to be elucidated. The present study aimed to investigate the effects of the HER‑2 gene on the biological behaviors of human malignant meningioma cells. The results demonstrated that downregulation of the expression of HER‑2 by small interfering RNA in human meningioma cells significantly inhibited cell motility and proliferation, led to cell cycle arrest at the G0/G1‑phase and increased early apoptosis. By contrast, the overexpression of HER‑2 group resulted in meningioma cell invasion, migration and proliferation being significantly enhanced, cell cycle was promoted at the G1/S‑phase and early apoptosis was decreased. Accordingly, the inhibition of HER‑2 also prevented the protein expression of PI3K and phosphorylated AKT. The results demonstrated that regulation of the HER‑2 gene can affect the proliferation, apoptosis, invasion and metastasis abilities of human meningioma cells in vitro. Furthermore, PI3K/AKT may contribute to the carcinogenesis and development of human meningiomas in combination with HER-2.

• Authors: Weijia Wang, Yi Tu, Shanshan Wang, Shan Xu, Linlin Xu, Yifeng Xiong, Jinhong Mei, Chunliang Wang
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 12 Issue 3 Pg. 3575-3582 (Sep 2015) ISSN: 1791-3004 [Electronic] Greece
• PMID: 25998419 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Small Interfering
• Phosphatidylinositol 3-Kinases
• ERBB2 protein, human
• Receptor, ErbB-2
• Proto-Oncogene Proteins c-akt

Topics

• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Humans
• Meningioma (genetics, metabolism, pathology)
• Neoplasm Invasiveness (genetics, pathology)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• RNA Interference
• RNA, Small Interfering (genetics)
• Receptor, ErbB-2 (genetics, metabolism)