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.