FoxM1B Is Overexpressed in Human Glioblastomas and Critically Regulates the Tumorigenicity of Glioma Cells
| Autor: | Suyun Huang, Bingbing Dai, Frederick F. Lang, Raymond Sawaya, Shin Hyuk Kang, Christopher E. Pelloski, Kenneth Aldape, Tongxin Xie, Feng Ju Huang, Keping Xie, Kechen Ban, Mingguang Liu |
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| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Transplantation Heterologous Mice Nude Astrocytoma Biology Mice Nude mouse Cell Line Tumor Glioma medicine SKP2 Animals Humans Protein Isoforms Cyclin D1 RNA Messenger S-Phase Kinase-Associated Proteins neoplasms Transcription factor Brain Neoplasms Forkhead Box Protein M1 Cancer Forkhead Transcription Factors Cell cycle medicine.disease biology.organism_classification nervous system diseases Oncology Cancer research FOXM1 Glioblastoma Cyclin-Dependent Kinase Inhibitor p27 Anaplastic astrocytoma |
| Zdroj: | Cancer Research. 66:3593-3602 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-05-2912 |
| Popis: | 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 SW1783 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. (Cancer Res 2006; 66(7): 3593-602) |
| Databáze: | OpenAIRE |
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