Screening for Candidate Brain Tumor Genes : Identifying Genes that Cooperate with Platelet-Derived Growth Factor in Glioma Development and Progression

摘要: Malignant primary brain tumors, gliomas, often overexpress both platelet-derived growth factor (PDGF) ligands and receptors providing an autocrine and/or paracrine boost to tumor growth. Glioblastoma multiforme (GBM) is the most frequent glioma. Its aggressive infiltrative renders it extremely difficult treat. Median survival after diagnosis currently only 14 months. The present thesis describes use of retroviral tagging identify candidate cancer-causing genes that cooperate with PDGF in formation. Newborn mice were injected intracerebrally a Moloney murine leukemia retrovirus carrying sis/PDGF-B oncogene replication competent helper virus. Brain tumors many characteristics human glioblastomas developed 13-42 weeks. Analysis proviral integrations identified almost 70 common insertion sites (CISs). These CISs named loci harbored known but also putative novel genes.An array over 15000 unique cDNAs was used screen for differentially expressed mouse compared normal brain. Known markers immature cells upregulated tumors. Short latency further distinguished as fast growing GBM-like. Long resembled slow-growing oligodendrogliomas contained significantly less short tumors.The gene Prkg2, encoding cGMP-dependent protein kinase II, targeted by insertions two Overexpression Prkg2 glioma cell lines led reduction colony formation, proliferation migration. A line expressing stem showed loss adhesion, G1 cycle arrest decreased activation signaling Akt upon stimulation cGMP analog activates protein. shows may be useful tool search genes.