Proliferation, hormonal responsiveness, and estrogen receptor content of MCF-7 human breast cancer cells grown in the short-term and long-term absence of estrogens.
Proliferation, hormonal responsiveness, and estrogen receptor content of MCF-7 human breast cancer cells grown in the short-term and long-term absence of estrogens.
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发表时间：
1987-08
期刊：
影响因子：
11.2
通讯作者：
B. Katzenellenbogen;Kari L. Kendra;M. Norman;Y. Berthois
中科院分区：
文献类型：
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作者：
B. Katzenellenbogen;Kari L. Kendra;M. Norman;Y. Berthois
我们研究了在没有雌激素的情况下短期和长期生长对MCF-7人乳腺癌细胞的增殖率以及雌激素和抗雌激素反应的影响。苯酚红的去除，组织培养介质中的pH指示剂，弱雌激素(Y.Berthois等人，Proc.娜塔莉。阿卡德。SCI。美国，83：2496-2500,1986)，立即减慢了细胞的增殖速度，并且MCF-7细胞在含有木炭葡聚糖处理的血清的无酚红培养液中生长长达1个月，保持了这种降低的细胞增殖速度。在这些短期的酚红撤除细胞中，雌二醇显著且可重复地刺激增殖，而抗雌激素则抑制雌激素刺激的增殖。抗雌激素本身表现为部分激动剂/拮抗剂；在低浓度时，它们对增殖的刺激作用很弱，但在高浓度时，它们没有刺激作用，当它们完全抑制雌激素刺激的增殖时。与短期去酚红的细胞相比，在明显完全无雌激素的情况下(无酚红，用木炭葡聚糖处理的小牛血清)维持几个月(5~6个月)的细胞表现出显著的基础增殖率；雌二醇不能进一步增加这种增殖率，但抗雌激素能抑制细胞的增殖。这种生长模式的变化与细胞雌激素受体水平增加3倍有关。尽管它们的基础生长率不同，但无论是在短期(小于1个月)或长期(大于6个月)缺乏雌激素的情况下生长的细胞，孕激素受体水平都非常低，而且在这两种情况下，雌二醇都显著提高了孕激素受体水平。因此，在长期无雌激素的条件下，雌激素对细胞增殖的刺激和对特定蛋白质合成(孕激素受体)的刺激是分离的。在长期没有雌激素的情况下生长的细胞中观察到的细胞增殖率的增加可能反映了生长因子产生的调节改变，或者对培养液中或由细胞本身产生的生长因子的敏感性改变。因此，这些乳腺癌细胞显著适应在无雌激素条件下的长期生长，这一观察结果可能与理解荷尔蒙反应型人类乳腺癌在体内的生长有关。
We have examined the effect of short-term and long-term growth in the absence of estrogens on the proliferation rate and estrogen and antiestrogen responsiveness of MCF-7 human breast cancer cells. The removal of phenol red, the pH indicator in tissue culture medium that is weakly estrogenic (Y. Berthois et al., Proc. Natl. Acad. Sci. USA, 83:2496-2500, 1986), immediately slows the cell proliferation rate, and MCF-7 cells grown in phenol red-free medium with charcoal dextran-treated serum for periods up to 1 mo maintain this reduced rate of cell proliferation. In these short-term phenol red-withdrawn cells, estradiol stimulates proliferation markedly and reproducibly, and antiestrogens inhibit estrogen-stimulated proliferation. Antiestrogens by themselves appear as partial agonists/antagonists; at low concentrations they stimulate proliferation weakly, but they show no stimulation at the high concentrations where they fully inhibit estrogen-stimulated proliferation. In contrast to the short-term phenol red-withdrawn cells, cells maintained for several months (5 to 6 mo) in the apparently complete absence of estrogens (no phenol red, with charcoal dextran-treated calf serum) show a markedly increased basal rate of cell proliferation; estradiol is unable to increase this rate of proliferation further, but antiestrogens are able to decrease proliferation. This change in growth pattern is associated with a 3-fold increase in cellular estrogen receptor levels. Despite their differing basal growth rates, cells grown in either the short-term (less than 1 mo) or long-term (greater than 6 mo) absence of estrogens both have progesterone receptor levels that are very low and, in both cases, estradiol increases progesterone receptor levels markedly. Thus, under long-term estrogen-free conditions, there is a dissociation between the stimulation of cell proliferation and of specific protein synthesis (progesterone receptor) by estrogen. The increase in the cell proliferation rate observed in cells grown in the long-term absence of estrogen may reflect altered regulation of growth factor production or altered sensitivity to growth factors in the medium or produced by the cells themselves. Hence, these breast cancer cells adapt significantly to long-term growth in estrogen-free conditions, an observation that may be relevant to understanding the growth of hormone-responsive human breast cancers in vivo.