p190RhoGAP can act to inhibit PDGF-induced gliomas in mice: a putative tumor suppressor encoded on human chromosome 19q13.3.
Brain-Neoplasms, Cell-Differentiation, Cells-Cultured, Chromosomes-Human-Pair-19, DNA-Binding-Proteins, Down-Regulation, GTPase-Activating-Proteins, Genes-Tumor-Suppressor, Glioma, Guanine-Nucleotide-Exchange-Factors, Intermediate-Filament-Proteins, Mice-Inbred-Strains, Nerve-Tissue-Proteins, Nuclear-Proteins, Oligodendroglioma, Phthalazines, Platelet-Derived-Growth-Factor, Pyridines, Repressor-Proteins, Retroviridae
Genes Dev 2003 Feb; 17(4):476-87.
p190RhoGAP and Rho are key regulators of oligodendrocyte differentiation. The gene encoding p190RhoGAP is located at 19q13.3 of the human chromosome, a locus that is deleted in 50%-80% of oligodendrogliomas. Here we provide evidence that p190RhoGAP may suppress gliomagenesis by inducing a differentiated glial phenotype. Using a cell culture model of autocrine loop PDGF stimulation, we show that reduced Rho activity via p190RhoGAP overexpression or Rho kinase inhibition induced cellular process extension, a block in proliferation, and reduced expression of the neural precursor marker nestin. In vivo infection of mice with retrovirus expressing PDGF and the p190 GAP domain caused a decreased incidence of oligodendrogliomas compared with that observed with PDGF alone. Independent experiments revealed that the retroviral vector insertion site in 3 of 50 PDGF-induced gliomas was within the p190RhoGAP gene. This evidence strongly suggests that p190 regulates critical components of PDGF oncogenesis and can act as a tumor suppressor in PDGF-induced gliomas by down-regulating Rho activity.
Wolf, R M.; Draghi, N; Liang, X; Dai, C; Uhrbom, L; Eklof, C; Westermark, B; Holland, E C.; and Resh, M D., "p190RhoGAP can act to inhibit PDGF-induced gliomas in mice: a putative tumor suppressor encoded on human chromosome 19q13.3." (2003). Faculty Research 2000 - 2009. 934.