ARS | Publication request: Marek's Disease Is a Natural Model for Lymphomas Overexpressing Hodgkin's Disease Antigen (Cd30)

Submitted to: Proceedings Of The National Academy Of Sciences
Publication Acceptance Date: September 21, 2004
Publication Date: September 21, 2004
Publisher's URL: www.pnas.org/cgi/doi/10.1073/pnas.0305789101
Citation: Burgess, S.C., Young, J.R., Baaten, B.J., Hunt, L., Ross, L.N., 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. 101(38):13879-13884.

Interpretive Summary: Marek's disease (MD), a virus induced cancer-like disease of chickens, is considered as a major disease problem in commercial poultry. Marek's disease virus (MDV), a chicken herpesvirus, is the causative agent of MD. The objective of this research was to identify an animal model which is essential for elucidating the molecular mechanisms of carcinogenesis. We identify a cancer marker CD30 in MD lymphoma cells, which is similar to CD30 of human Hodgkin's lymphoma cells. We also found CD 30 expressed by MDV transformed lymphocytes correlates with expression of the MDV Meq cancer-like gene. Thus CD30 may be a component of a critical pathway involved in the formation of cancer cells. Specific anti-CD30 molecules occurred after infection of genetically MD-resistant chickens with oncogenic MDV, suggesting immunity to CD30 could play a role in MD lymphoma regression. This important information may help scientists in academia and industry understand the function of CD30 cancer marker in MD lymphoma eradication. This approach eventually will lead to a better control of the disease in poultry.

Technical 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 (CD30(hi)), a tumor necrosis factor receptor II family member. Here we show that chicken Marek's disease (MD) lymphoma cells are also CD30(hi) and are a unique natural model for CD30(hi) 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 Meq 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.