JCV T-antigen interacts with the neurofibromatosis type 2 gene product in a transgenic mouse model of malignant peripheral nerve sheath tumors.
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. Oncogene (2004) 23, 5459-5467. doi:10.1038/sj.onc.1207728 Published online 10 May 2004
Shollar
Danielle
D
Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, 1900 North 12th Street, Philadelphia, PA 19122, USA.
Del Valle
Luis
L
Khalili
Kamel
K
Otte
Jessica
J
Gordon
Jennifer
J
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D007577:JC Virus / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D018317:Nerve Sheath Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D025581:Neurofibromin 2 / Q000378:metabolism*
D000957:Antigens, Viral, Tumor; D025581:Neurofibromin 2