The molecular and genetic basis of cancer will be studied using avian leukosis viruses and chickens as a model system. In vivo oncogenicity tests will be used to define viral genes that encode the induction of a high incidence of lymphoma or the induction of a high incidence of osteopetrosis and to define host genes that determine susceptibility to the induction of lymphomas and erythroblastosis. Tumor material acquired from the oncogenicity tests will be used to indentify host genes that are targets for cancer induction by insertional mutagenesis. The organization and expression of these genes will be examined in normal and diseased tissue. A novel model for the life cycle of ALVs that induce a high incidence of osteopetrosis will be tested. DNAs from selected tumors will be analyzed for their ability to transform NIH/3T3 cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA027223-06
Application #
3167540
Study Section
(SSS)
Project Start
1980-01-01
Project End
1986-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Worcester Foundation for Biomedical Research
Department
Type
DUNS #
City
Shrewsbury
State
MA
Country
United States
Zip Code
Taglienti-Sian, C A; Banner, B; Davis, R J et al. (1993) Induction of renal adenocarcinoma by a nonmutated erbB oncogene. J Virol 67:1132-6
Robinson, H L; Ramamoorthy, L; Collart, K et al. (1993) Tissue tropism of avian leukosis viruses: analyses for viral DNA and proteins. Virology 193:443-5
Theroux, S J; Taglienti-Sian, C; Nair, N et al. (1992) Increased oncogenic potential of ErbB is associated with the loss of a COOH-terminal domain serine phosphorylation site. J Biol Chem 267:7967-70
Robinson, H L; Foster, R G; Blais, B P et al. (1992) 5' avian leukosis virus sequences and osteopetrotic potential. Virology 190:866-71
Nair, N; Davis, R J; Robinson, H L (1992) Protein tyrosine kinase activities of the epidermal growth factor receptor and ErbB proteins: correlation of oncogenic activation with altered kinetics. Mol Cell Biol 12:2010-6
Collart, K L; Aurigemma, R; Smith, R E et al. (1990) Infrequent involvement of c-fos in avian leukosis virus-induced nephroblastoma. J Virol 64:3541-4
Vijaya, S; Steffen, D L; Kozak, C et al. (1987) Dsi-1, a region with frequent proviral insertions in Moloney murine leukemia virus-induced rat thymomas. J Virol 61:1164-70
Vijaya, S; Steffen, D L; Robinson, H L (1986) Acceptor sites for retroviral integrations map near DNase I-hypersensitive sites in chromatin. J Virol 60:683-92
Robinson, H L; Gagnon, G C (1986) Patterns of proviral insertion and deletion in avian leukosis virus-induced lymphomas. J Virol 57:28-36
Robinson, H L; Reinsch, S S; Shank, P R (1986) Sequences near the 5' long terminal repeat of avian leukosis viruses determine the ability to induce osteopetrosis. J Virol 59:45-9

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