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Journal of Molecular Neuroscience

, Volume 50, Issue 1, pp 165–171 | Cite as

Expression of R132H Mutational IDH1 in Human U87 Glioblastoma Cells Affects the SREBP1a Pathway and Induces Cellular Proliferation

  • Jian Zhu
  • Gang Cui
  • Ming Chen
  • Qinian Xu
  • Xiuyun Wang
  • Dai Zhou
  • Shengxiang Lv
  • Linshan Fu
  • Zhong Wang
  • Jianling ZuoEmail author
Article

Abstract

Sterol regulatory element-binding protein-1a (SREBP1a) is a member of the SREBP family of transcription factors, which mainly controls homeostasis of lipids. SREBP1a can also activate the transcription of isocitrate dehydrogenase 1 (IDH1) by binding to its promoter region. IDH1 mutations, especially R132H mutation of IDH1, are a common feature of a major subset of human gliomas. There are few data available on the relationship between mutational IDH1 expression and SREBP1a pathway. In this study, we investigated cellular effects and SREBP1a pathway alterations caused by R132H mutational IDH1 expression in U87 cells. Two glioma cell lines, stably expressing mutational (U87/R132H) or wild type (U87/wt) IDH1, were established. A cell line, stably transfected with pcDNA3.1(+) (U87/vector), was generated as a control. Click-iT® EdU assay, sulforhodamine B assay, and wound healing assay respectively showed that the expression of R132H induced cellular proliferation, cell growth, and cell migration. Western blot revealed that SREBP1 was increased in U87/R132H compared with that in U87/wt. Elevated SREBP1a and several its target genes, but not SREBP1c, were detected by real-time polymerase chain reaction in U87/R132H. All these findings indicated that R132H mutational IDH1 is involved in the regulation of proliferation, growth, and migration of glioma cells. These effects may partially be mediated by SREBP1a pathway.

Keywords

Glioma Sterol regulatory element-binding protein (SREBP) Isocitrate dehydrogenase 1 (IDH1) Proliferation 

Notes

Acknowledgments

This work was supported by Jiangsu Province’s Outstanding Medical Academic Leader program (no. LJ201139).

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Jian Zhu
    • 1
  • Gang Cui
    • 2
  • Ming Chen
    • 3
  • Qinian Xu
    • 2
  • Xiuyun Wang
    • 2
  • Dai Zhou
    • 2
  • Shengxiang Lv
    • 4
  • Linshan Fu
    • 1
  • Zhong Wang
    • 2
  • Jianling Zuo
    • 2
    Email author
  1. 1.Department of NeurosurgeryThe Fourth Affiliated Hospital of Nantong University (The First People’s Hospital of Yancheng)YanchengPeople’s Republic of China
  2. 2.Department of NeurosurgeryThe First Affiliated Hospital of Soochow UniversitySuzhouPeople’s Republic of China
  3. 3.Department of RadiologyThe First Hospital of ChangzhouChangzhouPeople’s Republic of China
  4. 4.Department of GastroenterologyThe Second People’s Hospital of Huai’anHuai’anPeople’s Republic of China

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