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Expression analysis of genes involved in brain tumor progression driven by retroviral insertional mutagenesis in mice

Oncogene volume 24, pages 3896–3905 (2005)Cite this article

Abstract

Retroviral tagging previously identified putative cancer-causing genes in a mouse brain tumor model where a recombinant Moloney murine leukemia virus encoding the platelet-derived growth factor B-chain (MMLV/PDGFB) was intracerebrally injected in newborn mice. In the present study, expression analysis using cDNA arrays revealed several similarities of virus-induced mouse gliomas with human brain tumors. Brain tumors with short latency contained on average 8.0 retroviral insertions and resembled human glioblastoma multiforme (GBM) whereas long-latency gliomas were of lower grade, similar to human oligodendroglioma (OD) and had 2.3 insertions per tumor. Several known and novel genes of tumor progression or cell markers were differentially expressed between OD- and GBM-like tumors. Array and quantitative real-time PCR analysis demonstrated elevated expression similar to Pdgfrα of retrovirally tagged genes Abhd2, Ddr1, Fos, Ng2, Ppfibp1, Rad51b and Sulf2 in both glioma types compared to neonatal and adult normal brain. The retrovirally tagged genes Plekhb1, Prex1, Prkg2, Sox10 and 1200004M23Rik were upregulated in the tumors but had a different expression profile than Pdgfrα whereas Rap1gap, Gli1, Neurl and Camk2b were downregulated in the tumors. The present study accentuates the proposed role of the retrovirally tagged genes in PDGF-driven gliomagenesis and indicates that insertional mutagenesis can promote glioma progression.

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Acknowledgements

We thank the WCN Expression Array Facility, headed by Anders Isaksson at the Department of Genetics and Pathology, Uppsala University, for putting the microarray facility at our disposal. We are also grateful for using BASE and the LCB Data Warehouse platform at the Linnaeus Center of Bioinformatics, Uppsala University. This work was supported by grants from the Swedish Cancer Foundation, the Children's Cancer Foundation and the Swedish Foundation for Strategic Research.

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  1. The Rudbeck Laboratory, Department of Genetics and Pathology, University Hospital, SE-751 85, Uppsala, Sweden

    Fredrik K Johansson, Hanna Göransson & Bengt Westermark

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  1. Fredrik K Johansson
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  2. Hanna Göransson
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Correspondence to Bengt Westermark.

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Johansson, F., Göransson, H. & Westermark, B. Expression analysis of genes involved in brain tumor progression driven by retroviral insertional mutagenesis in mice. Oncogene 24, 3896–3905 (2005). https://doi.org/10.1038/sj.onc.1208553

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