Modulation by Estrogen and Growth Factors of Transforming Growth Factor-Alpha and Epidermal Growth Factor Receptor Expression in Normal and Malignant Human Mammary Epithelial Cells

A number of well-characterized growth factors, such as epidermal growth factor (EGF) and the insulin-like growth factors (IGFs), can stimulate the proliferation and modify the differentiation of normal and malignant rodent and human mammary epithelial cells (Salomon et al. 1986 a, c). For example, EGF or transforming growth factor-alpha (TGFa) can stimulate the lobulo-alveolar development of mouse mammary glands in organ culture or in vivo (Tonelli and Soroff 1980; Okamoto and Oka 1984; Vonderhaar 1987). In addition, EGF may perform a physiological role in the development of the mouse mammary gland during pregnancy and lactation and in the spontaneous formation of mammary tumors in mice (Okamoto and Oka 1984; Oka et al. 1987; Tsutsumi et al. 1987). Several of these growth factors, such as IGF-I, platelet-derived growth factor (PDGF), TGFa, and TGFs, have been found in the conditioned medium (CM) from several human breast cancer cell lines (Salomon et al. 1984; Dickson et al. 1986; Huff et al. 1986; Bronzert et al. 1987; Knabbe et al. 1987; Peres et al. 1987). The production of TGFa, IGF-I, and TGF/3 can be modulated by estrogens or anti-estrogens, suggesting that the growth-promoting effects of estrogen may be mediated in part by TGFa and/or IGF-I and that the growth-inhibitory effects of anti-estrogen may be mediated by TGF/3 (Dickson et al. 1985; Perroteau et al. 1986; Knabbe et al. 1987; Liu et al. 1987; Peres et al. 1987; Huff et al. 1988). However, it is still unclear whether these or other growth factors are present in mammary tumor cells in vivo and, if so, whether they are involved in the etiology of tumor development and progression. Likewise, there is little information on the distribution and level of expression of similar growth factors in normal mammary epithelial cells at specific times during the development of the mammary gland.