Acquisition of transforming properties by FYN, a normal SRC-related human gene.

The SRC gene is the prototype for a family of closely related genes whose products have protein-tyrosine kinase activity. We recently described another member of this family, designated FYN, whose cDNA was isolated from normal human fibroblasts. To examine the possible role of FYN as an oncogene, we investigated the effects of FYN overexpression on NIH 3T3 cells. Our findings demonstrate that normal FYN overexpression induces morphologic transformation and anchorage-independent growth. In addition, at relatively low frequency, FYN acquired properties of a dominant-acting oncogene capable of inducing the fully tumorigenic phenotype. Genetic changes associated with the conversion of normal FYN cDNA into a transforming gene with high focus-forming activity were localized to the carboxyl-terminal region of its translational product.