Abstract

Avian leukosis viruses (ALVs) and in vitro constructed recombinants of ALVs will be used to study the roles of viral and host genes in the induction of cancer. The molecular virology of four different virally induced cancers will be studied: B-cell lymphoma, erythroblastosis, angiosarcoma, and fibrosarcoma. The first specific aim is to define ALV sequences that determine lymphomogenic potential. These studies will focus on the roles of sequences near the 5' long terminal repeat (LTR) and at the 5' end of the env gene in cancer induction. These studies will also examine the role of deletions near the 5' LTR in the upregulation of c-myc transcription by ALV insertions. The second specific aim is to define the role of the C-terminal domain of the epidermal growth factor (EGF) receptor in the normal and malignant growth of erythroid, endothelial, and fibroblastic cells. These studies will define mutations in the C-terminal domain of the EGF receptor that determine the potential for viral-erbB genes to cause specific diseases. Studies will also be the C- terminal domain of the EGF receptor. The third specific aim is to define whether one or more than one gene determines the unusual susceptibility of inbred line 151 chickens to erythroblastosis induction by viral-erbB proteins encoding the complete C- terminus of the EGF receptor.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA027223-12
Application #
3167544
Study Section
Virology Study Section (VR)
Project Start
1988-01-01
Project End
1992-12-31
Budget Start
1991-01-01
Budget End
1992-12-31
Support Year
12
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
University of Massachusetts Medical School Worcester
Department
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655

  Publications

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
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
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
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
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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