Lung cancer induced in mice by the envelope protein of jaagsiekte sheep retrovirus (JSRV) closely resembles lung cancer in sheep infected with JSRV

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Lung cancer induced in mice by the envelope protein of jaagsiekte sheep retrovirus (JSRV) closely resembles lung cancer in sheep infected with JSRV

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dc.contributor.author Wooton, Sarah K. en_US
dc.contributor.author Metzger, Michael J. en_US
dc.contributor.author Hudkins, Kelly en_US
dc.contributor.author Alpers, Charles E. en_US
dc.contributor.author York, Denis en_US
dc.contributor.author DeMartini, James C. en_US
dc.contributor.author Miller, A. Dusty en_US
dc.date.accessioned 2010-04-21T15:54:27Z
dc.date.available 2010-04-21T15:54:27Z
dc.date.issued 2006 en_US
dc.identifier.citation Wootton S, Metzger M, Hudkins K, et al. Lung cancer induced in mice by the envelope protein of jaagsiekte sheep retrovirus (JSRV) closely resembles lung cancer in sheep infected with JSRV. Retrovirology. 2006;3(1):94. en_US
dc.identifier.other 10.1186/1742-4690-3-94 en_US
dc.identifier.uri http://www.retrovirology.com/content/3/1/94 en_US
dc.identifier.uri http://hdl.handle.net/1773/15761
dc.description Researcher. Authors Alpers and Miller are also UW professors/researchers. Seven authors. en_US
dc.description.abstract Background: Jaagsiekte sheep retrovirus (JSRV) causes a lethal lung cancer in sheep and goats. Expression of the JSRV envelope (Env) protein in mouse lung, by using a replication-defective adeno-associated virus type 6 (AAV6) vector, induces tumors resembling those seen in sheep. However, the mouse and sheep tumors have not been carefully compared to determine if Env expression alone in mice can account for the disease features observed in sheep, or whether additional aspects of virus replication in sheep are important, such as oncogene activation following retrovirus integration into the host cell genome. Results: We have generated mouse monoclonal antibodies (Mab) against JSRV Env and have used these to study mouse and sheep lung tumor histology. These Mab detect Env expression in tumors in sheep infected with JSRV from around the world with high sensitivity and specificity. Mouse and sheep tumors consisted mainly of well-differentiated adenomatous foci with little histological evidence of anaplasia, but at long times after vector exposure some mouse tumors did have a more malignant appearance typical of adenocarcinoma. In addition to epithelial cell tumors, lungs of three of 29 sheep examined contained fibroblastic cell masses that expressed Env and appeared to be separate neoplasms. The Mab also stained nasal adenocarcinoma tissue from one United States sheep, which we show was due to expression of Env from ovine enzootic nasal tumor virus (ENTV), a virus closely related to JSRV. Systemic administration of the AAV6 vector encoding JSRV Env to mice produced numerous hepatocellular tumors, and some hemangiomas and hemangiosarcomas, showing that the Env protein can induce tumors in multiple cell types. Conclusion: Lung cancers induced by JSRV infection in sheep and by JSRV Env expression in mice have similar histologic features and are primarily characterized by adenomatous proliferation of peripheral lung epithelial cells. Thus it is unnecessary to invoke a role for insertional mutagenesis, gene activation, viral replication, or expression of other viral gene products in sheep lung tumorigenesis, although these processes may play a role in other clinically less important sequelae of JSRV infection such as metastasis observed with variable frequency in sheep. en_US
dc.description.sponsorship Overall funding was primarily provided by a pilot and feasibility grant from the Fred Hutchinson Cancer Research Center. en_US
dc.language.iso en_US en_US
dc.subject en_US
dc.title Lung cancer induced in mice by the envelope protein of jaagsiekte sheep retrovirus (JSRV) closely resembles lung cancer in sheep infected with JSRV en_US
dc.type Article en_US


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