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JCV T-antigen interacts with the neurofibromatosis type 2 gene product in a transgenic mouse model of malignant peripheral nerve sheath tumors

Oncogene volume 23, pages 5459–5467 (2004)Cite this article

Abstract

The human polyomavirus, JC virus, has recently been associated with several human CNS tumors, including medulloblastomas and a broad range of glial-origin tumors. This ubiquitous virus is the causative agent of the rare demyelinating disease, progressive multifocal leukoencephalopathy in immunocompromised individuals. Expression of the viral protein, T-antigen, which possesses the ability to transform cells of neural origin, has been detected in human CNS tumors. In an effort to further understand the transforming potential of JCV T-antigen, transgenic mice expressing JCV T-antigen under the control of the Mad-4 promoter were generated. As described previously, approximately 50% of the animals developed pituitary tumors by 1 year of age. However, a small subset of the animals developed solid masses arising from the soft tissues surrounding the salivary gland, the sciatic nerve, and along the extremities that histologically resemble malignant peripheral nerve sheath tumors, rare neoplasms that occur in individuals with neurofibromatosis type 1 (NF1). JCV T-antigen was detected in tumor tissue by immunohistochemistry and immunoprecipitation/Western blotting, but not in normal tissues and was colocalized with NF2, the putative tumor suppressor protein associated with neurofibromatosis type 2, in the nucleus of some cells. In addition, T-antigen was co-precipitated with NF2, but not with NF1 protein, although NF1 was detectable in tumor tissue. Furthermore, precipitated immunocomplexes contained T-antigen, NF2, and p53, suggesting that these three proteins may form a ternary complex. The importance of these findings on mechanisms of T-antigen-mediated tumorigenesis and the pathogenesis of neurofibromatosis are discussed.

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Acknowledgements

We thank the members of the Center for Neurovirology and Cancer Biology for their helpful suggestions and sharing of reagents. In particular, we thank Dr Kamel Khalili for his generous support for our initial studies and for his continued insight and guidance. We thank Cynthia Schriver for editorial assistance. We thank Dr James Gusella for his generous gift of the NF2 cDNA and Dr Christos D Katsetos for his kind gift of mouse monoclonal anti-Class III β-tubulin antibody. This work was supported by grants awarded by the National Institutes of Health to KK and JG.

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  1. Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Philadelphia, 19122, PA, USA

    Danielle Shollar, Luis Del Valle, Kamel Khalili, Jessica Otte & Jennifer Gordon

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  1. Danielle Shollar
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  2. Luis Del Valle
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  3. Kamel Khalili
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Correspondence to Jennifer Gordon.

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Shollar, D., Valle, L., Khalili, K. et al. JCV T-antigen interacts with the neurofibromatosis type 2 gene product in a transgenic mouse model of malignant peripheral nerve sheath tumors. Oncogene 23, 5459–5467 (2004). https://doi.org/10.1038/sj.onc.1207728

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