Cell transformation by Int-2--a member of the fibroblast growth factor family

The sequence similarities between Int-2 and members of the fibroblast growth factor (FGF) family have prompted functional as well as structural comparisons with other FGFs. Here we examine the ability of int-2 sequences to induced morphological transformation of NIH3T3 cells, a characteristic property of the secreted FGFs, such as FGF-5 and Hst1/kFGF. Despite encoding a short signal sequence, which directs the product to the secretory pathway, mouse int-2 DNA is incapable of inducing foci of transformation in the standard transfection assay. However, when transfected cells are enriched by co-selection with the neomycin resistance gene, a proportion of the int-2-expressing cells display a transformed phenotype, including the ability to grow as colonies in soft agar and in defined medium. Analyses of int-2 RNA and protein in these cells suggest that transformation by int-2 may require a threshold level of expression, and that the subsequent phenotype is dependent on the level of int-2 protein present in the cells.