EFFECT ON TUMORIGENICITY AND METASTASIS OF TRANSFECTION OF A DIPLOID BENIGN RAT MAMMARY EPITHELIAL-CELL LINE WITH DNA CORRESPONDING TO THE MESSENGER-RNA FOR BASIC FIBROBLAST GROWTH-FACTOR

To examine the potential role of fibroblast growth factors (FGF) in tu morigenesis and metastasis, plasmid constructs containing the human ba sic FGF (bFGF) gene, with or without fusion to a secretory signal pept ide (IgbFGF), were transfected into the diploid rat mammary epithelial cell line Rama 37. All transfectants possessed multiple copies of the transfected cDNA, which was expressed as the corresponding mRNA and t he protein. The amount of bFGF protein was usually greater than the bF GF growth-stimulatory activity that could be recovered from the transf ected cells. Nevertheless, the amount of bFGF growth-stimulatory activ ity secreted by the IgbFGF transfectants (0.08-0.8 ng/ml/24 hr) was su fficient to induce growth in responsive cells. However, the transfecta nts themselves were refractory to stimulation by exogenously added bFG F, despite possessing a small number of high-affinity receptors for bF GF. When the bFGF or the IgbFGF transfectants were inoculated into the mammary fat pads of syngeneic rats, the tumour incidence was low (0-5 0%). However, when cells cultured from these tumours were inoculated i nto the fat pad of syngeneic rats, the tumour incidence was 100%. Tumo urs were in all cases benign and no metastases were observed. Our resu lts suggest that the role of bFGF in metastasis is not simply one of a utocrine/paracrine stimulation of cell growth and that other events ma y also be required. (C) 1996 Wiley-Liss, Inc.