Sox10 has a broad expression pattern in gliomas and enhances platelet-derived growth factor-B--induced gliomagenesis.
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-alpha. 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.
Ferletta
Maria
M
Department of Genetics and Pathology, Uppsala University, Rudbeck Laboratory C11, Dag Hammarskjoldsv 20, S-751 85 Uppsala, Sweden. Maria.Ferletta@genpat.uu.se
Uhrbom
Lene
L
Olofsson
Tommie
T
Pontén
Fredrik
F
Westermark
Bengt
B
D000818:Animals; D001254:Astrocytoma / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002645:Chickens; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D006609:High Mobility Group Proteins / Q000235:genetics*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics; D008545:Melanoma / Q000235:genetics; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D011401:Promoter Regions, Genetic; D055757:SOXE Transcription Factors; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D010982:Platelet-Derived Growth Factor; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; D014157:Transcription Factors