School of Biological Sciences, University of Reading, Hopkins Building, Whiteknights, Reading RG6 6UB, U.K.
Anticancer Res. 2014 Jan;34(1):99-105.
Efficacy of endocrine therapy is compromised when human breast cancer cells circumvent imposed growth inhibition. The model of long-term oestrogen-deprived MCF-7 human breast cancer cells has suggested the mechanism results from hypersensitivity to low levels of residual oestrogen.
MCF-7 cells were maintained for up to 30 weeks in phenol-red-free medium and charcoal-stripped serum with 10(-8) M 17β-oestradiol and 10 μg/ml insulin (stock 1), 10(-8) M 17β-oestradiol (stock 2), 10 μg/ml insulin (stock 3) or no addition (stock 4).
Loss of growth response to oestrogen was observed only in stock 4 cells. Long-term maintenance with insulin in the absence of oestradiol (stock 3) resulted in raised oestrogen receptor-alpha (ERα) levels (measured by western immunoblotting) and development of hypersensitivity (assayed by oestrogen-responsive reporter gene induction and dose response to oestradiol for proliferation under serum-free conditions), but with no loss of growth response to oestrogen.
Hypersensitivity can develop without any growth adaptation and therefore is not a prerequisite for loss of growth response in MCF-7 cells.
当人乳腺癌细胞规避施加的生长抑制时，内分泌治疗的疗效会受到影响。长期去雌激素剥夺的 MCF-7 人乳腺癌细胞模型表明，这种机制是由于对低水平残留雌激素的超敏反应所致。
MCF-7 细胞在无酚红培养基和活性炭处理血清中维持长达 30 周，其中含有 10(-8) M 17β-雌二醇和 10 μg/ml 胰岛素（储备 1）、10(-8) M 17β-雌二醇（储备 2）、10 μg/ml 胰岛素（储备 3）或无添加（储备 4）。
仅在储备 4 细胞中观察到对雌激素生长反应的丧失。长期维持无雌激素的胰岛素（储备 3）导致雌激素受体-α（ERα）水平升高（通过 Western 免疫印迹测量）和超敏反应的发展（通过雌激素反应报告基因诱导和无血清条件下增殖对雌二醇的剂量反应测定），但对雌激素的生长反应没有丧失。
超敏反应可以在没有任何生长适应的情况下发展，因此不是 MCF-7 细胞生长反应丧失的先决条件。
