PDGFB AND P53 IN BRAIN TUMORIGENESIS

摘要: Glioblastoma is the most common, and malignant form of brain tumor. It characterized by a rapid growth diffuse spread to surrounding tissue. The cell origin still not known, but experimental data suggest an from glial precursor or neural stem cell. Analysis human glioma tissue has revealed many genetic aberrations, among which mutations loss TP53 together with amplification over-expression PDGFRA are common. Many pathways that found mutated in gliomas, normally important regulating functions. We have investigated role p53 adult cells, protein expressed SVZ mice. Comparison neurosphere cultures derived wt Trp53-/mice showed cells lacking increased self-renewal capacity, proliferate faster display reduced apoptosis. Gene expression profiling differential genes, prominent being Cdkn1a (p21) was down-regulated Trp53-/neural cells. Mice do develop combination mutation/deletion other aberrations common gliomas all grades. generated transgenic mouse model mimicking glioblastoma, over-expressing PDGFB under GFAP promoter Trp53 transgene active both astrocytes. These mice developed tumors resembling glioblastoma at age 2-6 months. histopathological features such as pseudopalisading necrosis, microvascular proliferation pleomorphic nuclei. used same study before tumor formation. In PDGFB/Trp53-/brain we numbers Pdgf receptor alpha beta vessels areas where later developed. Neurosphere-forming were more widespread location including corpus callosum. Thus, vasculature affected excessive p53. This investigation provides new insights into roles P53 PDGF leads deregulation compartment SVZ. Expression NSCs astrocytes Trp53-/brain, expansion forming ability locations brain. As result forced changed eventually, high-grade develop. LIST OF PUBLICATIONS I. Meletis K, Wirta V, Hede SM, Nister M, Lundeberg J, Frisen J. suppresses Development. 2006;133:363-9. II. Hansson I, Afink GB, Eriksson A, Nazarenko Andrae Genove G, Westermark B, M. driven null background GLIA. 2009; 57: 1143-53 III. He X, Stem pretumorigenic Manuscript