This project focuses on how hormones and mammary tumor virus (MTV) genes intersect to transform a mammary cell. We have found an apparently new integration site for MTV in the Balb/c mouse genome that is common to precancerous hyperplasias (HAN) induced both by chemical and hormonal carcinogens. These HAN with common integrations display common abnormalities in end-point differentiation (EPD) that can be traced to specific hormones controlling specific events. We are proposing to isolate the gene adjacent to the favored integration site in HAN and to test the hypothesis that activation of this gene, via a glucocorticoid enhancer sequence of the integrating provirus, inactivates, by a trans-acting mechanism that impairs the commitment of a cell to EPD, multiple genes involved in EPD. Our experiments are designed to test the hypothesis first in HAN per se and then to transfect the cloned gene into normal mammary cells in cell culture to determine if the gene directly impairs commitment and results in transformation to HAN. If this gene does exert a direct effect, we will have a way to generate reagents to prevent HAN transformation. By analogy to c-onc, we would expect these reagents to be useful in man.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA044901-03
Application #
3187763
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1986-06-01
Project End
1989-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Oakland University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Rochester
State
MI
Country
United States
Zip Code
48309
Morris, V L; Rao, T R; Kozak, C A et al. (1991) Characterization of Int-5, a locus associated with early events in mammary carcinogenesis. Oncogene Res 6:53-63