Submitted to: Workshop on Molecular Pathogenesis of Marek's Disease and Avian Immunology
Publication Type: Abstract Only
Publication Acceptance Date: 10/11/2002
Publication Date: 10/11/2002
Citation: Levy, A.M., Xia, L., Izumiya, Y., Lee, L.F., Kung, H.J. 2002. Oncogenic transformation of chicken embryo fibroblasts by meq [abstract]. Workshop on Molecular Pathogenesis of Marek's Disease and Avian Immunology. p. 52. Interpretive Summary:
Technical Abstract: Marek's Disease Virus (MDV) serotype-1 is an oncogenic avian herpesvirus, causing lymphomas in susceptible chickens. Meq is a basic leucine zipper (bZIP) transcription factor, belonging to the Jun/Fos gene family that can bind to AP-1 sites and form dimers with different cellular molecules. Based on comparative genomic analyses with non-oncogenic serotypes of MDV, its persistent expression in tumors and in transformed cell lines, its biochemical properties and recent Meq-null mutant analyses (by S. Reddy), Meq is viewed as a strong candidate to be MDV oncogene. Previously it was shown that Meq is able to transform a rat embryo fibroblast cell line and protect the cells from apoptosis induced by various agents. The mechanisms of transformation remain, however, unclear. In the present study we wish to elucidate Meq's mechanisms of transformation in its natural host, the chicken, using the DF-1 immortalized chicken embryo fibroblasts cell line, stably transfected with a pCI-neo expression vector containing Meq cDNA. Meq expression in the cells had a dramatic effect on cell morphology, on cell-cycle progression and on soft-agar colony formation. After serum starvation of DF-1 cultures, Meq showed a clear ability to down-regulate apoptosis. Using chicken-gene spotted microarrays, we have found and later verified by RT-PCR, that Meq up-regulated the expression of antiapoptotic genes and of other onco-genes and down-regulated the expression of proapoptotic genes. Studies are underway to uncover the possible promoter binding sites and the cellular counterparts of Meq in DF-1 cells.