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Pituitary neoplasia induced by expression of human neurotropic polyomavirus, JCV, early genome in transgenic mice

Oncogene volume 19, pages 4840–4846 (2000)Cite this article

Abstract

In recent years, there has been mounting evidence pointing to the association of polyomaviruses with a wide range of human cancers. The human neurotropic polyomavirus, JCV, infecting greater than 75% of the human population produces a regulatory protein named T-antigen which is expressed at the early phase of viral lytic infection and plays a critical role in completion of the viral life cycle. Furthermore, this protein has the ability to transform neural cells in vitro and its expression has been detected in several human neural-origin tumors. To further investigate the oncogenic potential of the JCV early protein in vivo, transgenic mice expressing JCV T-antigen under the control of its own promoter were generated. Nearly 50% of the animals developed large, solid masses within the base of the skull by 1 year of age. Evaluation of the location as well as histological and immunohistochemical data suggest that the tumors arise from the pituitary gland. As T-antigen is known to interact with several cell cycle regulators, the neoplasms were analysed for the presence of the tumor suppressor protein, p53. Immunoprecipitation/Western blot analysis demonstrated overexpression of wild-type, but not mutant p53 within tumor tissue. In addition, co-immunoprecipitation established an interaction between p53 and T-antigen and overexpression of p53 downstream target protein, p21/WAF1. This report describes the analysis of inheritable pituitary adenomas induced by expression of the human polyomavirus, JCV T-antigen in transgenic mice where T-antigen disrupts the p53 pathway by binding to and sequestering wild-type p53. This animal model may serve as a useful tool to further evaluate mechanisms of tumorigenesis by JCV T-antigen.

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Acknowledgements

The authors wish to thank members of the Center for Neurovirology and Cancer Biology for their helpful suggestions and sharing of reagents. In particular we thank Dr Sidney Croul for insightful discussion and Carlos Lorenzana for technical assistance. We also thank Cynthia Schriver for editorial assistance. This work was made possible by grants awarded by the National Institutes of Health to K Khalili.

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  1. Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, 1900 North 12th Street, Room 203, Philadelphia, 199122, Pennsylvania, PA, USA

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

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  1. Jennifer Gordon
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Gordon, J., Del Valle, L., Otte, J. et al. Pituitary neoplasia induced by expression of human neurotropic polyomavirus, JCV, early genome in transgenic mice. Oncogene 19, 4840–4846 (2000). https://doi.org/10.1038/sj.onc.1203849

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