Marek's disease is a natural model for lymphomas overexpressing Hodgkin's disease antigen (CD30).
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.
Burgess
S C
SC
Department of Basic Science, College of Veterinary Medicine, Mississippi State University, P.O. Box 1600, Mississippi State, MS 39762-6100, USA. burgess@cvm.msstate.edu
Young
J R
JR
Baaten
B J G
BJ
Hunt
L
L
Ross
L N J
LN
Parcells
M S
MS
Kumar
P M
PM
Tregaskes
C A
CA
Lee
L F
LF
Davison
T F
TF
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000276:immunology; D002645:Chickens; D017124:Conserved Sequence; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006689:Hodgkin Disease / Q000235:genetics* / Q000276:immunology; D006801:Humans; D017730:Ki-1 Antigen / Q000235:genetics*; D008213:Lymphocyte Activation / Q000276:immunology; D025922:Mardivirus / Q000276:immunology*; D008380:Marek Disease / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010802:Phylogeny; D016415:Sequence Alignment; D015398:Signal Transduction / Q000276:immunology
D015703:Antigens, CD; D017730:Ki-1 Antigen