MCF-7 breast carcinoma cells overexpressing FGF-1 form vascularized, metastatic tumors in ovariectomized or tamoxifen-treated nude mice

Abstract

FGF-1 is expressed in a high proportion of breast tumors. While overexpression of FGF-4 in the MCF-7 breast carcinoma cell line confers the ability to form spontaneously metastasizing tumors in ovariectomized nude mice without estrogen supplementation and in mice that receive tamoxifen pellets, the response of a cell to individual FGFs can be controlled 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 human breast cancer carcinoma cells, previously transfected with bacterial beta-galactosidase, were retransfected with FGF-1 expression vectors. FGF-1 transfectants formed large, vascularized tumors in ovariectomized nude mice without estrogen supplementation as well as in mice that received tamoxifen pellets. Lymphatic and pulmonary micrometastases were detected as deposits of X-gal-stained cells as early as 17 days after cell inoculation whereas no metastases were detected in estrogen-supplemented mice bearing similar-sized control tumors. When compared with controls, both clonal and polyclonal populations of FGF-1 overexpressing cells exhibited increased anchorage-independent growth and decreased population doubling times in estrogen-depleted or 4-hydroxytamoxifen containing medium. These results suggest that FGF signaling may be important in the transition of breast cancer cells from hormone-dependent to hormone-independent and from nonmetastatic to metastatic.