The Cancer Biology Group at NIEHS focuses on early events in skin tumor development using a transgenic mouse model (TgAC). This model possesses a v-Ha-ras transgene under the regulation of a fetal globin promotor integrated at an ectopic site which confers a unique phenotype of inducible skin papillomas with a high rate of progression to invasive squamous and spindle cell neoplasms. The goals of our studies are to identify and characterize: 1) The cellular origin of the tumors and 2) critical genes which are involved in ras-mediated tumor induction and progression. Conventional cancer therapies have until recently depended on treatment of late stages of tumor growth and involved non-specific mechanisms of cellular injury. By focusing on understanding early events in tumor induction we hope to gain insights into targets for intervention that can more specifically inhibit cancer cell growth.