EARLY EVENTS--CHEMICAL CARCINOGEN INDUCED MAMMARY TUMOR

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The long-term objective of this grant application is to understand the cellular and molecular basis for mammary gland preneoplastic transformation. The essential biological characteristics of mammary preneoplasias have been adequately described, however the cell and molecular correlates of these properties are unknown. The recent description of appropriate methods to grow and chemically transform mammary epithelial cells in vitro and the explosive documentation of the existence and properties of proto- oncogenes provide new avenues to understand long sought after goals. In this application, the aims are to examine specific cellular and molecular properties which may be the basis for the observed properties of mammary preneoplasias. Specifically, mammary epithelial cells will be transformed in vitro in a collagen-extracellular matrix gel and the cells assayed for transformation properties in vivo. The treated cells will be examined for alterations in growth factor dependence, proto- oncogene expression (those proto-oncogenes that are homologues of hormone receptors), altered keratin expression as well as morphological types of preneoplasias.