Basic fibroblast growth factor induces a transformed phenotype in normal human melanocytes

Basic fibroblast growth factor (bFGF or FGF-2) is produced by nearly all me lanomas in vitro and in viva but not by normal melanocytes, which require e xogenous bFGF for growth, In this study, we transduced normal human melanoc ytes to overexpress two forms of bFGF: (bFGF-Long and bFGF-Short) using rep lication-deficient adenovirus 5 vectors. bFGF-Long induced the 17.8, 22.5, 23.1 and 24.2 kDa forms of bFGF, whereas bFGF-Short induced only the 17.8 k Da mature form. Growth of cultured melanocytes transduced with either vecto r was similar to that of nevus and melanoma cells and was independent of ex ogenous bFGF and of insulin/insulin-like growth factor 1, and cyclic AMP en hancers, requiring only phorbol ester as an exogenous mitogen, Like primary melanoma cells, transduced normal melanocytes grew anchorage independently in soft agar, When injected into the dermis of human skin grafted to mice, bFGF-transduced melanocytes proliferated for at least 20 days, whereas cel ls from control cultures showed poor survival and no proliferation. These r esults demonstrate that bFGF upregulation is a component in melanoma progre ssion.