Sox10 Has a Broad Expression Pattern in Gliomas and Enhances Platelet-Derived Growth Factor-B–Induced Gliomagenesis
2007 (English)In: Molecular Cancer Research, ISSN 1541-7786, E-ISSN 1557-3125, Vol. 5, no 9, 891-897 p.Article in journal (Refereed) Published
In a previously published insertional mutagenesis screen for candidate brain tumor genes in the mouse using a Moloney mouse leukemia virus encoding platelet-derived growth factor (PDGF)-B, the Sox10 gene was tagged in five independent tumors. The proviral integrations suggest an enhancer effect on Sox10. All Moloney murine leukemia virus/PDGFB tumors had a high protein expression of Sox10 independently of malignant grade or tumor type. To investigate the role of Sox10 in gliomagenesis, we used the RCAS/tv-a mouse model in which the expression of retroviral-encoded genes can be directed to glial progenitor cells (Ntv-a mice). Both Ntv-a transgenic mice, wild-type, and Ntv-a p19Arf null mice were injected with RCAS-SOX10 alone or in combination with RCAS-PDGFB. Infection with RCAS-SOX10 alone did not induce any gliomas. Combined infection of RCAS-SOX10 and RCAS-PDGFB in wild-type Ntv-a mice yielded a tumor frequency of 12%, and in Ntv-a Arf−/− mice the tumor frequency was 30%. This indicates that Sox10 alone is not sufficient to induce gliomagenesis but acts synergistically with PDGFB in glioma development. All induced tumors displayed characteristics of PNET-like structures and oligodendroglioma. The tumors had a strong and widely distributed expression of Sox10 and PDGFR-α. We investigated the expression of Sox10 in other human tumors and in a number of gliomas. The Sox10 expression was restricted to gliomas and melanomas. All glioma types expressed Sox10, and tumors of low-grade glioma had a much broader distribution of Sox10 compared with high-grade gliomas.
Place, publisher, year, edition, pages
2007. Vol. 5, no 9, 891-897 p.
Animals, Astrocytoma/genetics, Brain Neoplasms/*genetics/pathology, Chickens, DNA-Binding Proteins/*genetics, Gene Expression Regulation; Neoplastic, Glioblastoma/genetics, Glioma/*genetics/*pathology, High Mobility Group Proteins/*genetics, Humans, Intermediate Filament Proteins/genetics, Melanoma/genetics, Mice, Nerve Tissue Proteins/genetics, Platelet-Derived Growth Factor/*physiology, Promoter Regions (Genetics), Transcription Factors/*genetics
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-13093DOI: 10.1158/1541-7786.MCR-07-0113ISI: 000249512000003PubMedID: 17855658OAI: oai:DiVA.org:uu-13093DiVA: diva2:40863