FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells

Mingguang Liu, Bingbing Dai, Shin-Hyuk Kang, Kechen Ban, Feng Ju Huang, Frederick F. Lang, Kenneth D. Aldape, Tong Xin Xie, Christopher E. Pelloski, Keping Xie, Raymond Sawaya, Suyun Huang

Research output: Contribution to journalArticle

244 Citations (Scopus)

Abstract

The transcription factor Forkhead box M1 (FoxM1) is overexpressed in malignant glioma. However, the functional importance of this factor in human glioma is not known. In the present study, we found that FoxM1B was the predominant FoxM1 isoform expressed in human glioma but not in normal brain tissue. The level of FoxM1 protein expression in human glioma tissues was directly correlated with the glioma grade. The level of FoxM1 protein expression in human glioblastoma tissues was inversely correlated with patient survival. Enforced FoxM1B expression caused SW17S3 and Hs683 glioma cells, which do not form tumor xenografts, to regain tumorigenicity in nude mouse model systems. Moreover, gliomas that arose from FoxM1B-transfected anaplastic astrocytoma SW1783 cells displayed glioblastoma multiforme phenotypes. Inhibition of FoxM1 expression in glioblastoma U-87MG cells suppressed their anchorage-independent growth in vitro and tumorigenicity in vivo. Furthermore, we found that FoxM1 regulates the expression of Skp2 protein, which is known to promote degradation of the cell cycle regulator p27Kip1. These results showed that FoxM1 is overexpressed in human glioblastomas and contributes to glioma tumorigenicity. Therefore, FoxM1 might be a new potential target of therapy for human malignant gliomas.

Original languageEnglish
Pages (from-to)3593-3602
Number of pages10
JournalCancer Research
Volume66
Issue number7
DOIs
Publication statusPublished - 2006 Apr 1
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Liu, M., Dai, B., Kang, S-H., Ban, K., Huang, F. J., Lang, F. F., Aldape, K. D., Xie, T. X., Pelloski, C. E., Xie, K., Sawaya, R., & Huang, S. (2006). FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells. Cancer Research, 66(7), 3593-3602. https://doi.org/10.1158/0008-5472.CAN-05-2912