The overall goal of this project is the exploration and exploitation of the biology of retroviruses as a means to a deeper understanding of neoplastic change. The model system on which the majority of the proposed work is focused is the induction of lymphomas in the bursa of Fabricius of chickens by natural and genetically engineered retroviruses. Specific experiments are directed at exploring the role of specific oncogenes in the induction of the pre-neoplastic transformed follicle stage and in the progression from transformed follicles to more advanced neoplasms. Retroviral constructs bearing c-myc and ChBlym-1 genes will be prepared, evaluated in tissue culture systems and introduced into embryonic bursal stem cells by the technique of bursal transplantation. Preneoplastic lesions and advanced neoplasms induced by this methodology will be evaluated for the expression of the relevant oncogenes using nucleic acid and immunologic probes. The normal expression of these and other proto-oncogenes will be evaluated in bursal lymphocytes using a counterflow centrifugation technique to separate lymphocyte populations. In situ hybridization will be used to amplify results obtained by the physical separation technique. Evidence will be sought of physiological mitogenic stimulation of bursal lymphocytes during development. Proto-oncogenes other than c-myc, for example, c-fos which are normally activated by this process, and a number of other potentially interesting genes, will be tested for their effects in the bursal transplantation assay. Finally, an attempt will be made to develop retroviral constructs expressing anti-sense RNA which might be used to selectively inhibit oncogene expression in this in vivo system.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Virology Study Section (VR)
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Fred Hutchinson Cancer Research Center
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Neiman, Paul E; Elsaesser, Katrina; Loring, Gilbert et al. (2008) Myc oncogene-induced genomic instability: DNA palindromes in bursal lymphomagenesis. PLoS Genet 4:e1000132
Kimmel, Robert R; Agnani, Shivali; Yang, Yin et al. (2008) DNA copy-number instability in low-dose gamma-irradiated TK6 lymphoblastoid clones. Radiat Res 169:259-69
Kimmel, Robert R; Zhao, Lue Ping; Nguyen, Doan et al. (2006) Microarray comparative genomic hybridization reveals genome-wide patterns of DNA gains and losses in post-Chernobyl thyroid cancer. Radiat Res 166:519-31
Neiman, P E; Kimmel, R; Icreverzi, A et al. (2006) Genomic instability during Myc-induced lymphomagenesis in the bursa of Fabricius. Oncogene 25:6325-35
Neiman, Paul E; Burnside, Joan; Elsaesser, Katrina et al. (2006) Analysis of gene expression, copy number and palindrome formation with a Dt40 enriched cDNA microarray. Subcell Biochem 40:245-56
Burnside, Joan; Neiman, Paul; Tang, Jianshan et al. (2005) Development of a cDNA array for chicken gene expression analysis. BMC Genomics 6:13
Brown, Cheryl Y; Bowers, Sandra J; Loring, Gibert et al. (2004) Role of Mtd/Bok in normal and neoplastic B-cell development in the bursa of Fabricius. Dev Comp Immunol 28:619-34
Parghi, Sean S; Brandvold, Kimberly A; Bowers, Sandra J et al. (2004) Reduced Myc overexpression and normal B-cell differentiation mediate resistance to avian leukosis virus lymphomagenesis. Oncogene 23:4413-21
Black, Elizabeth J; Clair, Timothy; Delrow, Jeffrey et al. (2004) Microarray analysis identifies Autotaxin, a tumour cell motility and angiogenic factor with lysophospholipase D activity, as a specific target of cell transformation by v-Jun. Oncogene 23:2357-66
Cheng, Chun; Kimmel, Robert; Neiman, Paul et al. (2003) Array rank order regression analysis for the detection of gene copy-number changes in human cancer. Genomics 82:122-9

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