EXPRESSION OF HUMAN FIBROBLAST GROWTH FACTOR-II AND CELL-TRANSFORMATION - SOME PARADOXICAL ASPECTS

Human fibroblast growth factor 2 (FGF-2) is involved in various physio logical processes including developpement, wound healing, angiogenesis and malignant transformation. FGF-2 is expressed as four isoforms res ulting from alternative initiations of translation on the same mRNA, a t three CUG and one AUG start codons. These FGF-2 isoforms have distin ct intracellular localizations and can modify cell phenotype different ly. We have previously shown that FGF-2 expression of the nuclear loca lized CUGs initated forms led to immortalization of transfected cells when the cytoplasmic AUG initiated form transformed the same cells. He re we have analysed FGF-2 expression in various human cells by Western immunoblotting: different profiles of the four isoforms were observed , depending on the cell types. The CUG-initiated forms were mainly det ected in transformed cell lines but not in normal cell types that most ly overproduced the AUG initiated form. To understand the role of thes e different forms we have established HeLa and skin fibroblasts (SE) c ell lines constitutively expressing one or the other form. Surprisingl y the constitutive expression of the 18 kDa AUG initiated form inhibit ed the anchorage independent growth of HeLa transfected cells whereas it allowed colonies formation in soft agar of SF modified cells. We di scuss here the possibility that the oncogenic potential of FGF-2 lies in a physiological balance between the different isoforms.