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Oncogenic transformation by the jaagsiekte sheep retrovirus envelope protein

Oncogene volume 26, pages 789–801 (2007)Cite this article

Abstract

Retroviruses have played profound roles in our understanding of the genetic and molecular basis of cancer. Jaagsiekte sheep retrovirus (JSRV) is a simple retrovirus that causes contagious lung tumors in sheep, known as ovine pulmonary adenocarcinoma (OPA). Intriguingly, OPA resembles pulmonary adenocarcinoma in humans, and may provide a model for this frequent human cancer. Distinct from the classical mechanisms of retroviral oncogenesis by insertional activation of or virus capture of host oncogenes, the native envelope (Env) structural protein of JSRV is itself the active oncogene. A major pathway for Env transformation involves interaction of the Env cytoplasmic tail with as yet unidentified cellular adaptor(s), leading to the activation of PI3K/Akt and MAPK signaling cascades. Another potential mechanism involves the cell-entry receptor for JSRV, Hyaluronidase 2 (Hyal2), and the RON receptor tyrosine kinase, but the exact roles of these proteins in JSRV Env transformation remain to be better understood. Recently, a mouse model of lung cancer induced by JSRV Env has been developed, and the tumors in mice resemble those seen in sheep infected with JSRV and in humans. In this review, we summarize recent progress in our understanding the molecular mechanisms of oncogenic transformation by JSRV Env protein, and discuss the relevance to human lung cancer.

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Acknowledgements

We apologize to those colleagues whose original work is not cited due to space limitations. We thank Michael Lerman, Alla Danilkovitch-Miagkova and James DeMartini for collaborations and discussions. This work was supported by funds from the Canadian Institutes of Health Research and McGill University to S-L Liu, and grants from the United States National Institutes of Health and the Fred Hutchinson Cancer Research Center to AD Miller, S-L Liu is a Canada Research Chair in Virology and Gene Therapy.

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  1. Department of Microbiology and Immunology, McGill University, Montreal, Canada

    S-L Liu

  2. Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    A D Miller

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Liu, SL., Miller, A. Oncogenic transformation by the jaagsiekte sheep retrovirus envelope protein. Oncogene 26, 789–801 (2007). https://doi.org/10.1038/sj.onc.1209850

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