Murphy L J, Sutherland R L, Stead B, Murphy L C, Lazarus L
Cancer Res. 1986 Feb;46(2):728-34.
Epidermal growth factor (EGF) receptors are present in human breast cancer and probably mediate the effects of EGF and the autocrine effects of alpha-transforming growth factors, produced by breast cancer cells. Steroid hormones influence the growth of some human cancers, and both direct and indirect effects on cell proliferation have been proposed. One potential indirect effect of steroids would be to augment sensitivity to other endocrine and autocrine factors by up-regulation of their receptors. We therefore investigated the effects of various steroids on EGF receptor expression in T-47D, MCF-7, and BT 20 human mammary carcinoma cells in culture. Preincubation of T-47D cells for 24 h with a series of androgens, estrogens, glucocorticoids, and progestins resulted in a significant enhancement of specific 125I-EGF binding in the presence of progestins only. Increased binding of EGF was associated with neither a change in cell number nor changes in the specific binding of concanavalin A, insulin, or calcitonin but was accompanied by an increase in lactogenic receptor expression. When assayed at 20 degrees C, increased EGF binding was due to an increase in receptor number (33,380 +/- 7,410 sites/cell in control cultures; 67,460 +/- 20,330 sites/cell in cultures treated with 1 nM medroxyprogesterone acetate for 24 h; P less than 0.05) without a change in receptor affinity. Two- to 3-fold increases in receptor number were also apparent when binding was measured at 4 degrees C, indicating that the effect was due to an increase in expression of receptor at the cell surface rather than progestin effects on internalization and degradation. These data illustrate that the expression of EGF receptor in some breast cancer cells is regulated in part by mechanisms mediated via the progesterone receptor, since the effect was confined to progestins, potency among a series of progestins was correlated with their affinities for progesterone receptor, and sensitivity among the three cell lines studied was related to the presence and concentration of cellular progesterone receptor.
表皮生长因子（EGF）受体存在于人类乳腺癌中，可能介导EGF的作用以及乳腺癌细胞产生的α-转化生长因子的自分泌作用。类固醇激素会影响某些人类癌症的生长，并且有人提出了其对细胞增殖的直接和间接作用。类固醇的一种潜在间接作用可能是通过上调其受体来增强对其他内分泌和自分泌因子的敏感性。因此，我们研究了各种类固醇对培养的T-47D、MCF-7和BT 20人乳腺癌细胞中EGF受体表达的影响。用一系列雄激素、雌激素、糖皮质激素和孕激素对T-47D细胞进行24小时预孵育，结果仅在孕激素存在的情况下，特异性125I-EGF结合显著增强。EGF结合增加与细胞数量的变化以及伴刀豆球蛋白A、胰岛素或降钙素的特异性结合变化均无关，但伴随着催乳素受体表达的增加。在20℃下进行测定时，EGF结合增加是由于受体数量增加（对照培养物中为33,380±7,410个位点/细胞；用1 nM醋酸甲羟孕酮处理24小时的培养物中为67,460±20,330个位点/细胞；P＜0.05），而受体亲和力没有变化。当在4℃下测量结合时，受体数量也有2至3倍的增加，这表明该作用是由于细胞表面受体表达增加，而不是孕激素对内化和降解的作用。这些数据表明，某些乳腺癌细胞中EGF受体的表达部分受通过孕激素受体介导的机制调节，因为该作用仅限于孕激素，一系列孕激素中的效力与其对孕激素受体的亲和力相关，并且所研究的三种细胞系中的敏感性与细胞孕激素受体的存在和浓度有关。
