Marek's disease is a natural model for lymphomas overexpressing Hodgkin's disease antigen (CD30)
| Autor: | C. A. Tregaskes, Mark S. Parcells, L. N. J. Ross, Lucy F. Lee, Lawrence G. Hunt, Shane C. Burgess, B. J. G. Baaten, T. F. Davison, Pradeep Kumar, John R. Young |
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| Rok vydání: | 2004 |
| Předmět: |
CD30
Mardivirus Molecular Sequence Data Ki-1 Antigen Biology Lymphocyte Activation medicine.disease_cause Conserved sequence Mice Antigens CD immune system diseases hemic and lymphatic diseases Marek Disease medicine Animals Humans Neoplastic transformation Amino Acid Sequence Transcription factor Conserved Sequence Phylogeny Genetics Marek's disease Multidisciplinary integumentary system Biological Sciences medicine.disease biology.organism_classification Hodgkin Disease Lymphoma Gene Expression Regulation Neoplastic Molecular Weight Disease Models Animal Cell Transformation Neoplastic Cancer research Carcinogenesis Chickens Sequence Alignment Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 101:13879-13884 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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 CD30hiand are a unique natural model for CD30hilymphoma. 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 MDVMeqputative oncogene (ac-Junhomologue)in vivo. The chicken CD30 promoter has 15 predicted high-stringencyMeq-binding transcription factor recognition motifs, andMeqenhances transcription from the CD30 promoterin 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. |
| Databáze: | OpenAIRE |
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