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Author Notes:

E-mail Address : hgshu@emory.edu

The authors thank Zhaobin Zhang for assistance in intracranial injection of tumor cells.

Subjects:

Keywords:

  • glioblastoma
  • glioma
  • brain tumor
  • tumorigenesis
  • cyclooxygenase-2
  • Id1

COX-2 overexpression increases malignant potential of human glioma cells through Id1

Tools:

Journal Title:

Oncotarget

Volume:

Volume 5, Number 5

Publisher:

, Pages 1241-1252

Type of Work:

Article | Final Publisher PDF

Abstract:

Increased COX-2 expression directly correlates with glioma grade and is associated with shorter survival in glioblastoma (GBM) patients. COX-2 is also regulated by epidermal growth factor receptor signaling which is important in the pathogenesis of GBMs. However, COX-2 expression has not been previously shown to directly alter malignancy of GBMs. Id1 is a member of the helix-loop-helix (HLH) family of transcriptional repressors that act as dominant-negative inhibitors of basic-HLH factors. This factor has been shown to be regulated by COX-2 in breast carcinoma cells and recent studies suggest that Id1 may also be involved in the genesis/progression of gliomas. We now show that COX-2 increases the aggressiveness of GBM cells. GBM cells with COX-2 overexpression show increased growth of colonies in soft agar. Tumorigenesis in vivo is also increased in both subcutaneous flank and orthotopic intracranial tumor models. COX-2 overexpression induces Id1 expression in two GBM cell lines suggesting a role for Id1 in glioma transformation/tumorigenesis. Furthermore, we find direct evidence of a role for Id1 with significant suppression of in vitro transformation and in vivo tumorigenesis in COX-2-overexpressing GBM cells where Id1 has been knocked down. In fact, Id1 is even more efficient at enhancing transformation/tumorigenesis of GBM cells than COX-2. Finally, GBM cells with COX-2 or Id1 overexpression show greater migration/invasive potential and tumors that arise from these cells also display increased microvessel density, results in line with the increased malignant potential seen in these cells. Thus, COX-2 enhances the malignancy of GBM cells through induction of Id1.

Copyright information:

© 2014 Xu et al.

This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License ( http://creativecommons.org/licenses/by/3.0/), which permits making multiple copies, distribution, public display, and publicly performance, distribution of derivative works, provided the original work is properly cited. This license requires credit be given to copyright holder and/or author, copyright and license notices be kept intact.

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