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BIOLOGICAL SCIENCES / MEDICAL SCIENCES
Insulin-like growth factor binding protein 2 promotes glioma development and progression
*Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; and ¶Department of Neurosurgery, Memorial Sloan–Kettering Cancer Center, New York, NY 10021
Edited by Webster K. Cavenee, University of California at San Diego School of Medicine, La Jolla, CA, and approved May 29, 2007 (received for review April 4, 2007)
Overexpression of insulin-like growth factor binding protein 2 (IGFBP2) is associated with progression in many types of human cancer. In this study we used a glial-specific transgenic mouse model to examine the active role of IGFBP2 in tumorigenesis and progression. Our studies show that IGFBP2 coexpression results in progression to a higher-grade glioma in platelet-derived growth factor 
(PDGFB)-driven tumors. These anaplastic oligodendrogliomas are characterized by increased cellularity, vascular proliferation, small regions of necrosis, increased mitotic activity, and increased activation of the Akt pathway. Combined expression of IGFBP2 or Akt with K-Ras was required to form astrocytomas, indicating that activation of two separate pathways is necessary for gliomagenesis. In ex vivo experiments, blockade of Akt by an inhibitor led to decreased viability of cells coexpressing IGFBP2 versus PDGFB expression alone. Thus, this study provides definitive evidence that IGFBP2 plays a key role in activation of the Akt pathway and collaborates with K-Ras or PDGFB in the development and progression of two major types of glioma.
glial-specific transgenic mouse model | oligodendroglioma
Present address: Department of Gynecologic Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030.
Present address: Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030.
Present address: Tianjin Medical University, Tianjin General Hospital, Tianjin 300052, China.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0703145104/DC1.
||To whom correspondence may be addressed at: Department of Pathology, University of Texas M. D. Anderson Cancer Center, Unit 85, 1515 Holcombe Boulevard, Houston, TX 77030. E-mail: gfuller{at}mdanderson.org or wzhang{at}mdanderson.org
© 2007 by The National Academy of Sciences of the USA
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