Growth stimulation of human breast epithelial cells by basic fibroblast growth factor in serum‐free medium

Abstract

Growth-stimulating activities of basic and acidic fibroblast growth factors (FGFs) toward human breast epithelial cells were examined and compared with the mitogenic activity of bovine pituitary extract (BPE) by the use of a serum-free medium which contained epidermal growth factor, insulin, transferrin, hydrocortisone, ethanolamine, phosphoethanolamine, prolactin and prostaglandin. Addition of 1 ng/ml of basic FGF (bFGF) to the serum-free medium significantly enhanced the growth potential of epithelial cells derived from human breast carcinoma, and the number of cells grown for 7 days with bFGF was more than 1 1/2 times higher than that in the serum-free medium containing BPE instead of prolactin and prostaglandin. Growth responsiveness toward bFGF of epithelial cells derived from histologically non-malignant breast tissues was lower than that of carcinoma-derived cells, and the growth-stimulating activity of bFGF was lower than that of BPE, which could significantly enhance the growth potential of the cells. Contrary to bFGF, acidic FGF at 1 ng/ml had no significant effect on the growth potential of breast epithelial cells which had grown out from either carcinoma or non-malignant tissues. The present results suggest that bFGF is a putative growth-stimulating factor for human breast epithelial cells, especially for carcinoma-derived cells, and can substitute at least in part for BPE in serum-free monolayer culture of the cells.

Fibroblast growth factor overexpressing breast carcinoma cells as models of angiogenesis and metastasis

“…Although FGF-1 and FGF-4 have been shown to be angiogenic factors and endothelial cell mitogens [25], they are also mitogenic for fibroblasts and for some epithelial cells, including MCF-7 cells themselves [29][30][31]43]. As mentioned, FGFRs are widely distributed on many cell types, including MCF-7 cells.…”

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

“…However, FGFs can be mitogenic for breast epithelial cells (Valverius et al, 1990;Imagawa et al, 1994;Takahashi et al, 1989) Lehtola et al, 1992). We therefore used anchorage-dependent and anchorage-independent in vitro growth assays in estrogen-depleted and antiestrogen-containing media to test whether FGF-1 overexpression had any autocrine eects on the growth of transfected cells.…”

Expression of basic fibroblast growth factor, FGFR1 and FGFR2 in normal and malignant human breast, and comparison with other normal tissues

“…Mitogenic effects have been noted on both MCF-7 cells and on immortalised mammary epithelial cells derived from breast reduction mammoplaasty (Valverius et al, 1990). Primary monolayer cultures of breast epithelial cells grown out of fragmented biopsy tissue were reported to show a modest response to bFGF (more pronounced in cancer than in nonmalignant samples) but were unaffected by aFGF (Takahashi et al, 1989). As none of these studies were concerned with the identity of the receptor, it is not yet clear which of the sub-types are involved.…”

“…Acidic FGF expression is largely confined to neural tissues (Maxwell et al, 1991) whereas bFGF is ubiquitously distributed in normal human tissues (CordonCardo et al, 1990), and in neural and squamous carcinomas, melanomas, osteosarcomas and hemangiomas (Takahashi et al, 1990;Shulze-Osthoff et al, 1990). It is mitogenic for cultured mammary epithelial cells (Takahashi et al, 1989;Briozzo et al, 1991) and stimulates plasminogen activator (Lopez et al, 1986) which has been implicated in tumour invasion . Basic FGF has been immunolocalised in myoepithelial cells in benign breast and around intraduct carcinomas but was not detected in cancer cells (Gomm et al, 1991).…”