| Abstract: |
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 β (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. © 2007 by The National Academy of Sciences of the USA. |
| Keywords: |
signal transduction; protein kinase b; controlled study; cancer growth; nonhuman; glioma; cancer grading; cell proliferation; mitosis; animal cell; animals; mice; animal tissue; cell survival; cells, cultured; gene overexpression; animal experiment; animal model; enzyme activation; vascularization; mice, inbred balb c; mice, inbred c57bl; carcinogenesis; gene transfer; transgenic mouse; mus musculus; mice, transgenic; cell transformation, neoplastic; disease progression; proto-oncogene proteins c-akt; cell line, transformed; oligodendroglioma; ras proteins; animals, newborn; k ras protein; ex vivo study; astrocytoma; protein determination; anaplastic carcinoma; complementary dna; chickens; protein kinase b inhibitor; platelet derived growth factor b; tissue necrosis; glial-specific transgenic mouse model; somatomedin binding protein 2; insulin-like growth factor binding protein 2
|
