MCF-7 BREAST-CARCINOMA CELLS OVEREXPRESSING FGF-1 FORM VASCULARIZED, METASTATIC TUMORS IN OVARIECTOMIZED OR TAMOXIFEN-TREATED NUDE-MICE

FGF-1 is expressed in a high proportion of breast tumors, While overex pression of FGF-4 in the MCF-7 breast carcinoma cell line confers the ability to form spontaneously metastasizing tumors in ovariectomized n ude mice without estrogen supplementation and in mice that receive tam oxifen pellets, the response of a cell to individual FGFs can be contr olled at multiple levels, and the significance of FGF-1 expression in human breast tumors is uncertain, To study the role of FGF-1, MCF-7 hu man breast cancer carcinoma cells, previously transfected with bacteri al beta-galactosidase, were retransfected with FGF-1 expression vector s, FGF-1 transfectants formed large, vascularized tumors in ovariectom ized nude mice without estrogen supplementation as web as in mice that received tamoxifen pellets, Lymphatic and pulmonary micrometastases w ere detected as deposits of X-gal-stained cells as early as 17 days af ter cell inoculation whereas no metastases were detected in estrogen-s upplemented mice bearing similar-sized control tumors, When compared w ith controls, both clonal and polyclonal populations of FGF-1 overexpr essing cells exhibited increased anchorage-independent growth and decr eased population doubling times in estrogen-depleted or 4-hydroxytamox ifen containing medium, These results suggest that FGF signaling may b e important in the transition of breast cancer cells from hormone-depe ndent to hormone-independent and from nonmetastatic to metastatic.