RHO-GENE AMPLIFICATION AND MALIGNANT TRANSFORMATION

Our previous studies have shown that overexpression of the protooncogene rho in Rat-1 and 3T3 fibroblasts resulted in colonies that displayed altered growth regulation (8). In this report we demonstrate that the human rho gene is capable of eliciting neoplastic growth of an established cell line - Rat Rhol DHFR, rat fibroblast cells that are stably transfected to overexpress the full-length cDNA rho A. The established transfectant lines grow to a high saturation density in monolayer cultures and, when maintained and postconfluence, developed dense foci. The overexpression of rho A cDNA altered not only the in vitro growth properties of Rat-1 cells but also their in vivo behavior. Injection of these transfected cells into athymic nude mice resulted in the formation of tumors. Introduction of rho A cDNA with the selectable dihydrofolate reductase marker into rat embryo fibroblasts resulted in the outgrowth of few rho transfected colonies. These colonies expressed high levels of rho cDNA and could proliferate for at least 40 generations. Our results show a positive correlation between overexpression of the human rho gene and tumorigenicity. © 1990.