FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells.
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 p27(Kip1). 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.
Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Mingguang
M
Liu
Bingbing
B
Dai
Shin-Hyuk
SH
Kang
Kechen
K
Ban
Feng-Ju
FJ
Huang
Frederick F
FF
Lang
Kenneth D
KD
Aldape
Tong-xin
TX
Xie
Christopher E
CE
Pelloski
Keping
K
Xie
Raymond
R
Sawaya
Suyun
S
Huang
D000818:Animals; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism; D014183:Transplantation, Heterologous
D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C491524:Foxm1 protein, mouse; D020033:Protein Isoforms; D012333:RNA, Messenger; D044786:S-Phase Kinase-Associated Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27