p190RhoGAP can act to inhibit PDGF-induced gliomas in mice: a putative tumor suppressor encoded on human chromosome 19q13.3.
2003 (English)In: Development, Genes and Evolution, ISSN 0949-944X, E-ISSN 1432-041X, Vol. 17, no 4, 476-487 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2003. Vol. 17, no 4, 476-487 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-64200DOI: 10.1101/gad.1040003PubMedID: 12600941OAI: oai:DiVA.org:uu-64200DiVA: diva2:92111