The objective of our continuing research program is to understand the requirements for growth and functional differentiation of human mammary epithelial cells (HMEC) and to provide urgently needed cell culture model systems for research on breast cancer and other aspects of mammary physiology. We have already achieved long-term growth of HMEC, equivalent to that of normal human fibroblasts, in a serum-free medium supplemented with pituitary extract, and shorter term growth in a defined medium. Our research during the next three years will emphasize the following areas: 1) Refinement of growth media to obtain better growth of dense cultures and long term growth without undefined supplements; 2) Development of media and conditions that favor expression of differentiated properties by cultured HMEC, with initial emphasis on achieving a lactation-like state; 3) Careful cellular characterization to verify that the cells growing in our media really are normal, human, epithelial, and mammary in origin, together with development of specific assays for careful evaluation of mammary-specific differentiated function; 4) Analysis of growth regulation and possible stem cell relationships in cultured HMEC; and 5) Analysis of the roles of other breast cell types in growth and differentiation of HMEC, and of ways to make growth of HMEC from a mixed inoculum as selective as possible. These studies will provide important new basic science information. At the present time, there is no type of normal glandular epithelial cell from humans (or from any other vertebrate species) for which the complete set of growth requirements is known. Our research will provide that information together with data on requirements for expression of differentiated properties. In addition, the model systems that are being developed will be of major value to research in many diverse areas of cell biology, embryology, endocrinology, developmental biology, carcinogenesis, cancer therapy, and cancer prevention.
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