Abstract

This program on the biology of RNA tumor viruses consists of studies in three principal systems: murine leukemia virus (MuLV), murine mammary tumor virus (MTV), and feline leukemia virus (FeLV). The common objective in all of these studies is to determine the nature of the host-virus interactions leading to oncogenesis and to compare roles of exogenous and endogenous viruses in this process.
The aims are to investigate: (1) Phenotypes of MuLVs and MuLV-specific macromolecules of radiation leukemias, (2) the relation of these MuLVs to induction of the TL antigen in leukemias induced by radiation or chemical treatment, (3) the role of genetic recombination in altering infectivity and leukemogenicity of MuLVs, (4) the role of endogenous MuLV-specified molecules in lymphoid cell differentiation, (5) the functions of MuLV proteins in virion formation, (6) the immune responses of cats to FeLV infection and FeLV-induced leukemogenesis, and to experimental viral vaccines, (7) the biochemical nature of FeLV- and RD114-specific cell-surface antigens (e.g., FOCMA), (8) the comparative biochemistry of FeLV RNA genomes, intracellular transcripts and proviral integration sites, (9) the detailed molecular nature of the initial RNA transcripts of integrated type-C viral genomes, (10) the biochemical relationships of horizontally and vertically transmitted MTV genomes, together with linkage studies on proviral DNA, and (11) biochemical characteristics of MTV-specific proteins and cell-surface antigens (e.g., the ML antigen). It is hoped that these studies will lead to development of new models for how RNA tumor virus genes and gene products function in oncogenesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA016599-17
Application #
3092718
Study Section
Special Emphasis Panel (SRC (Q1))
Project Start
1979-03-01
Project End
1994-02-28
Budget Start
1991-03-01
Budget End
1992-02-29
Support Year
17
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Tam, Wayne; Hughes, Stephen H; Hayward, William S et al. (2002) Avian bic, a gene isolated from a common retroviral site in avian leukosis virus-induced lymphomas that encodes a noncoding RNA, cooperates with c-myc in lymphomagenesis and erythroleukemogenesis. J Virol 76:4275-86
Tam, W; Ben-Yehuda, D; Hayward, W S (1997) bic, a novel gene activated by proviral insertions in avian leukosis virus-induced lymphomas, is likely to function through its noncoding RNA. Mol Cell Biol 17:1490-502
Dealy, C N; Roth, A; Ferrari, D et al. (1993) Wnt-5a and Wnt-7a are expressed in the developing chick limb bud in a manner suggesting roles in pattern formation along the proximodistal and dorsoventral axes. Mech Dev 43:175-86
Stocker, K M; Brown, A M; Ciment, G (1993) Gene transfer of lacZ into avian neural tube and neural crest cells by retroviral infection of grafted embryonic tissues. J Neurosci Res 34:135-45
Ramakrishna, N R; Brown, A M (1993) Wingless, the Drosophila homolog of the proto-oncogene Wnt-1, can transform mouse mammary epithelial cells. Dev Suppl :95-103
Manova, K; Huang, E J; Angeles, M et al. (1993) The expression pattern of the c-kit ligand in gonads of mice supports a role for the c-kit receptor in oocyte growth and in proliferation of spermatogonia. Dev Biol 157:85-99
Eisenberg, L M; Ingham, P W; Brown, A M (1992) Cloning and characterization of a novel Drosophila Wnt gene, Dwnt-5, a putative downstream target of the homeobox gene distal-less. Dev Biol 154:73-83
Jue, S F; Bradley, R S; Rudnicki, J A et al. (1992) The mouse Wnt-1 gene can act via a paracrine mechanism in transformation of mammary epithelial cells. Mol Cell Biol 12:321-8
Koo, H M; Brown, A M; Kaufman, R J et al. (1992) A spleen necrosis virus-based retroviral vector which expresses two genes from a dicistronic mRNA. Virology 186:669-75
Mikawa, T; Borisov, A; Brown, A M et al. (1992) Clonal analysis of cardiac morphogenesis in the chicken embryo using a replication-defective retrovirus: I. Formation of the ventricular myocardium. Dev Dyn 193:11-23

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