The goal of our research is to understand the process by which simian virus 40 transforms cells in culture and causes tumors in animals. To this end, we have constructed and characterized an SV4O mutant, T147D, that lacks many of the SV4O viral replication functions, but which is still able to transform. Because of these properties, T147D should be useful in identifying SV4O functions essential for transformation. Oncogenic transformation involves a number of alterations in cell structure, function, and metabolism, and it is unlikely that the SV4O oncoprotein, T antigen, could cause all these changes directly. It is more probable that T antigen acts indirectly by modulating the expression of key cellular genes, and that this altered pattern of gene expression results, at least in part, in the transformed phenotype. For this reason, it would be of great interest to identify the cellular genes whose expression is modulated by SV4O transformation. We have used subtractive hybridization to identify a cellular gene, D46, that is up-regulated in T147D transformants and in a variety of other oncogene-expressing cells. We propose to characterize this gene further in order to elucidate its role in SV4O-mediated transformation, and to use subtractive hybridization and mRNA differential display to identify other cellular genes that also may be important for transformation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA053322-03
Application #
2095281
Study Section
Virology Study Section (VR)
Project Start
1994-08-01
Project End
1998-07-31
Budget Start
1996-08-01
Budget End
1998-07-31
Support Year
3
Fiscal Year
1996
Total Cost
Indirect Cost
Name
University of Colorado at Boulder
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
Boulder
State
CO
Country
United States
Zip Code
80309
Sompayrac, L; Jane, S; Lorper, M et al. (1998) A 47-amino-acid fragment of SV40 T antigen represses transcription from human GSTalpha promoters. Virology 249:275-85
Sompayrac, L (1997) SV40 and adenovirus may act as cocarcinogens by downregulating glutathione S-transferase expression. Virology 233:130-5
Sompayrac, L; Jane, S; Danna, K J (1996) Reduced levels of alpha1(XI) procollagen mRNA in SV40-transformed cells. Virology 218:412-6
Sompayrac, L; Jane, S; Burn, T C et al. (1995) Overcoming limitations of the mRNA differential display technique. Nucleic Acids Res 23:4738-9