Animal models for validating melanoma chemopreventive agents are unavailable. In this proposal, we describe the development of a human skin equivalent model for chemopreventive agent validation. Loss of function analysis will be utilized to validate that known genes that inhibit (E-cadherin) or promote (N-cadherin) melanoma formation impact tumor progression in our tissue model. Real time multiphoton microscopy will be utilized to measure the impact of individual genes or chemopreventive agents on the behavior of normal or neoplastic melanocytes In Vivo. Eventually, this skin equivalent model will obviate the need for laboratory animals in preclinical testing of melanoma chemopreventive agents.