Marek's disease is a natural model for lymphomas overexpressing Hodgkin's disease antigen (CD30)

S. C. Burgess, J. R. Young, B. J.G. Baaten, L. Hunt, L. N.J. Ross, M. S. Parcells, P. M. Kumar, C. A. Tregaskes, L. F. Lee, T. F. Davison

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77 Scopus citations

Abstract

Animal models are essential for elucidating the molecular mechanisms of carcinogenesis. Hodgkin's and many diverse non-Hodgkin's lymphomas overexpress the Hodgkin's disease antigen CD30 (CD30hi), a tumor necrosis factor receptor II family member. Here we show that chicken Marek's disease (MD) lymphoma cells are also CD30hi and are a unique natural model for CD30hi lymphoma. Chicken CD30 resembles an ancestral form, and we identify a previously undescribed potential cytoplasmic signaling domain conserved in chicken, human, and mouse CD30. Our phylogeneic analysis defines a relationship between the structures of human and mouse CD30 and confirms that mouse CD30 represents the ancestral mammalian gene structure. CD30 expression by MD virus (MDV)-transformed lymphocytes correlates with expression of the MDV Meq putative oncogene (a c-Jun homologue) in vivo. The chicken CD30 promoter has 15 predicted high-stringency Meq-binding transcription factor recognition motifs, and Meg enhances transcription from the CD30 promoter in vitro. Plasma proteomics identified a soluble form of CD30. CD30 overexpression is evolutionarily conserved and defines one class of neoplastic transformation events, regardless of etiology. We propose that CD30 is a component of a critical intracellular signaling pathway perturbed in neoplastic transformation. Specific anti-CD30 Igs occurred after infection of genetically MD-resistant chickens with oncogenic MDV, suggesting immunity to CD30 could play a role in MD lymphoma regression.

Original languageEnglish (US)
Pages (from-to)13879-13884
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number38
DOIs
StatePublished - Sep 21 2004
Externally publishedYes

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    Burgess, S. C., Young, J. R., Baaten, B. J. G., Hunt, L., Ross, L. N. J., Parcells, M. S., Kumar, P. M., Tregaskes, C. A., Lee, L. F., & Davison, T. F. (2004). Marek's disease is a natural model for lymphomas overexpressing Hodgkin's disease antigen (CD30). Proceedings of the National Academy of Sciences of the United States of America, 101(38), 13879-13884. https://doi.org/10.1073/pnas.0305789101