Insulin-like growth factor binding protein 2 promotes glioma development and progression.
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 beta (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.
Dunlap
Sarah M
SM
Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Celestino
Joseph
J
Wang
Hua
H
Jiang
Rongcai
R
Holland
Eric C
EC
Fuller
Gregory N
GN
Zhang
Wei
W
D000818:Animals; D000831:Animals, Newborn; D001254:Astrocytoma / Q000235:genetics / Q000473:pathology; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002478:Cells, Cultured; D002645:Chickens; D018450:Disease Progression; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D018631:ras Proteins / Q000502:physiology
D018971:Insulin-Like Growth Factor Binding Protein 2; D051057:Proto-Oncogene Proteins c-akt; D018631:ras Proteins