This project is aimed at characterizing parameters important to the growth and differentiation of melanocytes, and their significance to critical properties of transformed melanocytes, termed malignant melanoma, with respect to their outgrowth and metastasis. our studies have identified, isolated and characterized three different melanogenic enzymes that interact to regulate the quality and quantity of pigment produced within melanocytes. These proteins share significant sequence homology and belong to a new family of tyrosinase-related genes that are specifically expressed by mammalian melanocytes. In combination with a melanogenic inhibitor currently being studied which affects those catalytic activities, mammalian melanogenesis is strictly regulated. Our studies have also continued the characterization of melanoma-specific antigens abnormally expressed on transformed melanocytes. At least two of those antigens are related to normal melanocyte constituents which are aberrantly expressed or synthesized by the transformed cells; those antigens are recognized by the tumor-bearing host as foreign. Monoclonal antibodies to those antigens have now been raised which cross-react with human melanoma cells; these highly specific reagents are proving useful in immunodiagnostic tests, and in experimental anti-metastatic assays in murine models.
