The specific aims are to analyze the role of tissue interactions (mammary fat pad stroma, adjacent normal mammary parenchyma, and tumor cells) and hormones in promoting the growth of ovarian-dependent rat mammary tumors induced by the chemical carcinogen, 7,12-dimethylbenz(a)anthracene (DMBA). The major methods include surgical preparation of mammary fat pads of syngeneic hosts for transplantation sites, tumor transplantation, cell dissociation, and organ culture. The growth behavior of mammary tumors will be evaluated in gland-free and intact mammary fat pads under various physiological, hormonal, and dietary conditions in vivo and in vitro. The long-term study should provide insight into local and systemic mechanisms that promote the expression and growth of phenotypically-labile mammary tumors. These studies are of relevance to human breast cancer, where a major problem is tumor recurrence even after long periods of dormancy. Analysis of the factors that promote mammary tumor growth from a latent state should help in the development of strategies to prevent the emergence of dormant tumors. Among the scientific disciplines involved are oncology, experimental breast carcinogenesis, pathology, endocrinology, and developmental biology.
