Overexpression of septin 7 suppresses glioma cell growth

J Neurooncol. 2010 Jul;98(3):329-40. doi: 10.1007/s11060-009-0092-1. Epub 2009 Dec 25.

Abstract

Our previous study demonstrated that SEPT7 was downregulated at mRNA level in human gliomas. This study is to further examine the expression of SEPT7 in glioma samples and characterizes its role on cell cycle progression and growth of glioma cells. mRNA and protein expression of SEPT7 were detected by RT-PCR, immunohistochemical staining, and western blot analysis in human glioma specimens and normal brain tissues. A pcDNA3-SEPT7 expression plasmid was constructed and transfected into human glioblastoma cell line U251, and cell proliferation and apoptosis were examined. The growth of established U251 and TJ905 subcutaneous xenograft gliomas was measured in nude mice treated with pcDNA3-SEPT7 and U251 xenograft tumors treated with SEPT7 siRNA. SEPT7 expression is negatively correlated with the increase of glioma grade. Overexpression of SEPT7 is able to inhibit cell proliferation and arrest cell cycle progression in the G0/G1 phase both in vitro and in vivo. Knocking down further the already low endogenous expression of SEPT7 in U251 xenograft tumors with siRNA leads to faster tumor growth compared with control tumors. This study demonstrates that SEPT7 is involved in gliomagenesis and suppresses glioma cell growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Apoptosis / physiology
  • Brain / metabolism
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Caspase 3 / metabolism
  • Cell Cycle / physiology
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Proliferation
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Disease Models, Animal
  • Flow Cytometry / methods
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic / physiology*
  • Glial Fibrillary Acidic Protein / metabolism
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • In Situ Nick-End Labeling / methods
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation / mortality
  • Neoplasm Transplantation / pathology
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / pharmacology
  • Septins
  • Time Factors
  • Tissue Array Analysis / methods
  • Transfection / methods

Substances

  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Glial Fibrillary Acidic Protein
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • RNA, Small Interfering
  • Caspase 3
  • GTP-Binding Proteins
  • SEPTIN7 protein, human
  • Septins