Avian leukosis virus induces a bursal dependent B cell lymphoma in the chicken. A rare histopathological lesion, the transformed follicle, appears in the bursa shortly after infection. It has been proposed that this lesion is a preneoplastic stage required for the development of the lymphoma. The long range goal of this project is to define the biochemical characteristics that distinguish the preneoplastic cell from the normal cell. The preneoplastic cell represents an intermediate stage of neoplastic development that deserved considerable study. Analysis of the transformed follicle should provide information fundamental to an appreciation of the biochemical and physiological conditions that increase the propensity of a cell to develop into a tumor. The cells within the ALV-induced transformed follicle will be characterized by in situ hybridization and immunochemical analysis in order to identify the presence of specific mRNAs and proteins. A recombinant retroviral vector will be used to evaluate the hypothesis that the expression of c-myc results in the formation of the preneoplastic event. cDNA hybridization probes specific for the transformed follicle and the tumor will be developed by subtractive hybridization in order to identify clones within a cDNA library. These genes, expressed preferentially in preneoplastic or neoplastic tissue, will be characterized and the sequences encoding the protein inserted into retroviral vectors. Virus prepared from these vectors will be used in an in vivo assay to assess the functional significance of the expression of these genes in establishing the preneoplastic state.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
7R01CA032295-08
Application #
3170272
Study Section
Pathology B Study Section (PTHB)
Project Start
1983-06-01
Project End
1991-12-31
Budget Start
1990-09-15
Budget End
1991-12-31
Support Year
8
Fiscal Year
1990
Total Cost
Indirect Cost
Name
West Virginia University
Department
Type
Schools of Medicine
DUNS #
191510239
City
Morgantown
State
WV
Country
United States
Zip Code
26506
Pizer, E S; Baba, T W; Humphries, E H (1992) Activation of the c-myb locus is insufficient for the rapid induction of disseminated avian B-cell lymphoma. J Virol 66:512-23
Filardo, E J; Humphries, E H (1991) An avian retrovirus expressing chicken pp59c-myc possesses weak transforming activity distinct from v-myc that may be modulated by adjacent normal cell neighbors. J Virol 65:6621-9
Carlson, L M; McCormack, W T; Postema, C E et al. (1990) Templated insertions in the rearranged chicken IgL V gene segment arise by intrachromosomal gene conversion. Genes Dev 4:536-47
Buerstedde, J M; Reynaud, C A; Humphries, E H et al. (1990) Light chain gene conversion continues at high rate in an ALV-induced cell line. EMBO J 9:921-7
Humphries, E H; Filardo, E J (1990) The transforming activity of PP59C-MYC is weaker than that of v-myc. Curr Top Microbiol Immunol 166:259-65
Kim, S; Humphries, E H; Tjoelker, L et al. (1990) Ongoing diversification of the rearranged immunoglobulin light-chain gene in a bursal lymphoma cell line. Mol Cell Biol 10:3224-31
Pizer, E; Humphries, E H (1989) RAV-1 insertional mutagenesis: disruption of the c-myb locus and development of avian B-cell lymphomas. J Virol 63:1630-40
Humphries, E H; Barth, C F; Pizer, E (1988) The development of three distinct avian B cell lymphomas. Curr Top Microbiol Immunol 141:58-66
Humphries, E H; Baba, T W (1986) Restrictions that influence avian leukosis virus-induced lymphoid leukosis. Curr Top Microbiol Immunol 132:215-20
Baba, T W; Humphries, E H (1986) Selective integration of avian leukosis virus in different hematopoietic tissues. Virology 155:557-66

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