1887

Abstract

Ovine pulmonary adenocarcinoma, caused by jaagsiekte sheep retrovirus (JSRV), is a naturally occurring retrovirus-induced pulmonary neoplasm of sheep. We report here that expression of the JSRV gene is sufficient to transform an avian embryo fibroblast cell line, DF-1. DF-1 cells transfected with an avian sarcoma–leukaemia retroviral expression vector containing the JSRV gene [pRCASBP(A)-J:] exhibited changes consistent with transformation, including contraction and rounding of cells with formation of dense foci. Transfection with a reporter construct expressing the green fluorescent protein did not induce morphological changes in DF-1 cells, eliminating the possibility that the vector, the transfection protocol or culturing techniques were responsible for the transformed phenotype. When pRCASBP(A)-J:-transfected cells were inoculated into nude mice, tumours formed, verifying that the DF-1 cells were tumorigenic. Analysis of the JSRV gene revealed a conserved tyrosine (597) and methionine (600) residue in the cytoplasmic tail within the transmembrane domain of the envelope, which creates a known binding site of SH2 domains in the p85 subunit of phosphatidylinositol 3-kinase. However, when this tyrosine residue was mutated to serine or alanine, transformation was not affected. Furthermore, mutation of the methionine residue to valine or leucine also failed to eliminate JSRV -mediated transformation. These results are in contrast to mutational analysis performed in JSRV -transformed murine NIH-3T3 cells in which both the tyrosine and methionine residues are necessary for transformation. These findings suggest that more than one mechanism may be involved in JSRV -mediated transformation.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-83-11-2733
2002-11-01
2020-01-17
Loading full text...

Full text loading...

/deliver/fulltext/jgv/83/11/0832733a.html?itemId=/content/journal/jgv/10.1099/0022-1317-83-11-2733&mimeType=html&fmt=ahah

References

  1. Alian, A., Sela-Donenfeld, D., Panet, A. & Eldor, A. ( 2000; ). Avian hemangioma retrovirus induces cell proliferation via the envelope (env) gene. Virology 276, 161-168.[CrossRef]
    [Google Scholar]
  2. Bai, J., Bishop, J. V., Carlson, J. O. & DeMartini, J. C. ( 1999; ). Sequence comparison of JSRV with endogenous proviruses: envelope genotypes and a novel ORF with similarity to a G-protein coupled receptor. Virology 258, 333-343.[CrossRef]
    [Google Scholar]
  3. Barsky, S. H., Cameron, R., Osann, K. E., Tomita, D. & Holmes, E. C. ( 1994; ). Rising incidence of bronchioloalveolar lung carcinoma and its unique clinicopathologic features. Cancer 73, 1163-1170.[CrossRef]
    [Google Scholar]
  4. Bonne, C. ( 1939; ). Morphological resemblance of pulmonary adenomatosis (jaagsiekte) in sheep and certain cases of cancer of the lung in man. American Journal of Cancer 35, 491.
    [Google Scholar]
  5. Chang, H. W., Aoki, M., Fruman, D., Auger, K. R., Bellacosa, A., Tsichlis, P. N., Cantley, L. C., Roberts, T. M. & Vogt, P. K. ( 1997; ). Transformation of chicken cells by the gene encoding the catalytic subunit of PI 3-kinase. Science 276, 1848-1850.[CrossRef]
    [Google Scholar]
  6. Datta, S. R., Brunet, A. & Greenberg, M. E. ( 1999; ). Cellular survival: a play in three Akts. Genes & Development 13, 2905-2927.[CrossRef]
    [Google Scholar]
  7. DeMartini, J. C. & York, D. F. ( 1997; ). Retrovirus-associated neoplasms of the respiratory system of sheep and goats. Ovine pulmonary carcinoma and enzootic nasal tumor. Veterinary Clinics of North America: Food Animal Practice 13, 55-70.
    [Google Scholar]
  8. DeMartini, J. C., Rosadio, R. H., Sharp, J. M., Russell, H. I. & Lairmore, M. D. ( 1987; ). Experimental coinduction of type D retrovirus-associated pulmonary carcinoma and lentivirus-associated lymphoid interstitial pneumonia in lambs. Journal of the National Cancer Institute 79, 167-177.
    [Google Scholar]
  9. DeMartini, J. C., Bishop, J. V., Allen, T. E., Jassim, F. A., Sharp, J. M., De Las Heras, M., Voelker, D. R. & Carlson, J. O. ( 2001; ). Jaagsiekte sheep retrovirus provirus clone JSRVJS7, derived from the JS7 lung tumor cell line, induces ovine pulmonary carcinoma and is integrated into the surfactant protein A gene. Journal of Virology 75, 4239-4246.[CrossRef]
    [Google Scholar]
  10. Fan, H. ( 1997; ). Leukemogenesis by Moloney murine leukemia virus: a multistep process. Trends in Microbiology 5, 74-82.[CrossRef]
    [Google Scholar]
  11. Fang, C., Choi, E., Nie, L. & Li, J. P. ( 1998; ). Role of the transmembrane sequence of spleen focus-forming virus gp55 in erythroleukemogenesis. Virology 252, 46-53.[CrossRef]
    [Google Scholar]
  12. Federspiel, M. J. & Hughes, S. H. ( 1997; ). Retroviral gene delivery. Methods in Cell Biology 52, 179-214.
    [Google Scholar]
  13. Fisher, G. H., Orsulic, S., Holland, E., Hively, W. P., Li, Y., Lewis, B. C., Williams, B. O. & Varmus, H. E. ( 1999; ). Development of a flexible and specific gene delivery system for production of murine tumor models. Oncogene 18, 5253-5260.[CrossRef]
    [Google Scholar]
  14. Ginzburg, H. M., Vokes, E. E. & Raben, A. ( 1996; ). Non-small cell lung cancer. In Cancer: Principles and Practice of Oncology , pp. 858-911. Edited by V. T. DeVita, S. Hellman & S. A. Rosenberg. Philadelphia:Lippincott–Raven.
  15. Himly, M., Foster, D. N., Bottoli, I., Iacovoni, J. S. & Vogt, P. K. ( 1998; ). The DF-1 chicken fibroblast cell line: transformation induced by diverse oncogenes and cell death resulting from infection by avian leukosis viruses. Virology 248, 295-304.[CrossRef]
    [Google Scholar]
  16. Kobayashi, M., Nagata, S., Iwasaki, T., Yanagihara, K., Saitoh, I., Karouji, Y., Ihara, S. & Fukui, Y. ( 1999; ). Dedifferentiation of adenocarcinomas by activation of phosphatidylinositol 3-kinase. Proceedings of the National Academy of Sciences, USA 96, 4874-4879.[CrossRef]
    [Google Scholar]
  17. Kung, H. J. & Liu, J. ( 1997; ). Retroviral oncogenesis. In Viral Pathogenesis , pp. 235-257. Edited by N. Nathanson. Philadelphia:Lippincott–Raven.
  18. Kung, H. J., Boerkoel, C. & Carter, T. H. ( 1991; ). Retroviral mutagenesis of cellular oncogenes: a review with insights into the mechanisms of insertional activation. Current Topics in Microbiology and Immunology 171, 1-25.
    [Google Scholar]
  19. Liebow, A. A. ( 1960; ). Bronchiolo-alveolar carcinoma. Advances in Internal Medicine 10, 329-358.
    [Google Scholar]
  20. Maeda, N., Palmarini, M., Murgia, C. & Fan, H. ( 2001; ). Direct transformation of rodent fibroblasts by Jaagsiekte sheep retrovirus DNA. Proceedings of the National Academy of Sciences, USA 98, 4449-4454.[CrossRef]
    [Google Scholar]
  21. Moore, S. M., Rintoul, R. C., Walker, T. R., Chilvers, E. R., Haslett, C. & Sethi, T. ( 1998; ). The presence of a constitutively active phosphoinositide 3-kinase in small cell lung cancer cells mediates anchorage-independent proliferation via a protein kinase B and p70s6k-dependent pathway. Cancer Research 58, 5239-5247.
    [Google Scholar]
  22. Morris, D. W. & Cardiff, R. D. ( 1987; ). Multistep model of mouse mammary tumor development. Advances in Viral Oncology 7, 123-140.
    [Google Scholar]
  23. Palmarini, M. & Fan, H. ( 2001; ). Retrovirus-induced ovine pulmonary adenocarcinoma, an animal model for lung cancer. Journal of the National Cancer Institute 93, 1603-1614.[CrossRef]
    [Google Scholar]
  24. Palmarini, M., Fan, H. & Sharp, J. M. ( 1997; ). Sheep pulmonary adenomatosis: a unique model of retrovirus-associated lung cancer. Trends in Microbiology 5, 478-483.[CrossRef]
    [Google Scholar]
  25. Palmarini, M., Sharp, J. M., De Las Heras, M. & Fan, H. ( 1999; ). Jaagsiekte sheep retrovirus is necessary and sufficient to induce a contagious lung cancer in sheep. Journal of Virology 73, 6964-6972.
    [Google Scholar]
  26. Palmarini, M., Hallwirth, C., York, D., Murgia, C., De Oliveira, T., Spencer, T. & Fan, H. ( 2000; ). Molecular cloning and functional analysis of three type D endogenous retroviruses of sheep reveal a different cell tropism from that of the highly related exogenous Jaagsiekte sheep retrovirus. Journal of Virology 74, 8065-8076.[CrossRef]
    [Google Scholar]
  27. Palmarini, M., Maeda, N., Murgia, C., De Fraja, C., Hofacre, A. & Fan, H. ( 2001; ). A phosphatidylinositol 3-kinase docking site in the cytoplasmic tail of the Jaagsiekte sheep retrovirus transmembrane protein is essential for envelope-induced transformation of NIH 3T3 cells. Journal of Virology 75, 11002-11009.[CrossRef]
    [Google Scholar]
  28. Payment, P. & Trudel, M. (1993). Methods and Techniques in Virology. New York: Marcel Dekker.
  29. Perk, K. & Hod, I. ( 1982; ). Sheep lung carcinoma: an epidemic analogue of a human neoplasm. Journal of the National Cancer Institute 69, 747-750.
    [Google Scholar]
  30. Platt, J. A., Kraipowich, N., Villafane, F. & DeMartini, J. C. ( 2002; ). Alveolar type II cells expressing Jaagsiekte sheep retrovirus capsid protein and surfactant proteins are the predominant neoplastic cell type in ovine pulmonary adenocarcinoma. Veterinary Pathology 39, 341-352.[CrossRef]
    [Google Scholar]
  31. Rai, S. K., Duh, F. M., Vigdorovich, V., Danilkovitch-Miagkova, A., Lerman, M. I. & Miller, A. D. ( 2001; ). Candidate tumor suppressor HYAL2 is a glycosylphosphatidylinositol (GPI)-anchored cell-surface receptor for Jaagsiekte sheep retrovirus, the envelope protein of which mediates oncogenic transformation. Proceedings of the National Academy of Sciences, USA 98, 4443-4448.[CrossRef]
    [Google Scholar]
  32. Rosadio, R. H., Lairmore, M. D., Russell, H. I. & DeMartini, J. C. ( 1988; ). Retrovirus-associated ovine pulmonary carcinoma (sheep pulmonary adenomatosis) and lymphoid interstitial pneumonia. I. Lesion development and age susceptibility. Veterinary Pathology 25, 475-483.[CrossRef]
    [Google Scholar]
  33. Sambrook, J., Fritsch, E. F. & Maniatis, T. (1989). Molecular Cloning: a Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  34. Schaefer-Klein, J., Givol, I., Barsov, E. V., Whitcomb, J. M., Vanbrocklin, M., Foster, D. N., Federspiel, M. J. & Hughes, S. H. ( 1998; ). The EV-O-derived cell line DF-1 supports the efficient replication of avian leukosis-sarcoma viruses and vectors. Virology 248, 305-311.[CrossRef]
    [Google Scholar]
  35. Sharp, J. M., Angus, K., Gray, E. & Scott, F. ( 1983; ). Rapid transmission of sheep pulmonary adenomatosis (Jaagsiekte) in young lambs. Archives of Virology 78, 89-95.[CrossRef]
    [Google Scholar]
  36. Shayesteh, L., Lu, Y., Kuo, W. L., Baldocchi, R., Godfrey, T., Collins, C., Pinkel, D., Powell, B., Mills, G. B. & Gray, J. W. ( 1999; ). PIK3CA is implicated as an oncogene in ovarian cancer. Nature Genetics 21, 99-102.[CrossRef]
    [Google Scholar]
  37. Shin, S. I., Freedman, V. H., Risser, R. & Pollack, R. ( 1975; ). Tumorigenicity of virus-transformed cells in nude mice is correlated specifically with anchorage independent growth in vitro. Proceedings of the National Academy of Sciences, USA 72, 4435-4439.[CrossRef]
    [Google Scholar]
  38. Wu, A. H., Yu, M. C., Thomas, D. C., Pike, M. C. & Henderson, B. E. ( 1988; ). Personal and family history of lung disease as risk factors for adenocarcinoma of the lung. Cancer Research 48, 7279-7284.
    [Google Scholar]
  39. York, D. F., Vigne, R., Verwoerd, D. W. & Querat, G. ( 1992; ). Nucleotide sequence of the Jaagsiekte retrovirus, an exogenous and endogenous type D and B retrovirus of sheep and goats. Journal of Virology 66, 4930-4939.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-83-11-2733
Loading
/content/journal/jgv/10.1099/0022-1317-83-11-2733
Loading

Data & Media loading...

Most cited articles

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error