LITHIUM-STIMULATED PROLIFERATION AND ALTERATION OF PHOSPHOINOSITIDE METABOLITES IN MCF-7 HUMAN BREAST-CANCER CELLS
LITHIUM-STIMULATED PROLIFERATION AND ALTERATION OF PHOSPHOINOSITIDE METABOLITES IN MCF-7 HUMAN BREAST-CANCER CELLS
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DOI：
10.1002/jcp.1041650116
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发表时间：
1995-10-01
影响因子：
5.6
通讯作者：
CURRAN, EM
中科院分区：
文献类型：
--
作者：
WELSHONS, WV;ENGLER, KS;CURRAN, EM
用于治疗双相精神疾病的锂可以刺激组织培养中许多细胞的增殖。 MCF-7 人类乳腺癌细胞也对 EGF 和雌激素有反应，LiCl (1-5 mM) 在人类锂治疗过程中遇到的浓度范围内会刺激其增殖。生长刺激是锂特有的；铷、钾和钠则没有表现出这样的效果。在抗雌激素存在的情况下，锂刺激激素依赖性乳腺癌细胞MCF-7、ZR-75-1和T47D的生长，但不刺激激素非依赖性MDA-MB-231细胞或非雌激素依赖性MCF-7细胞克隆的生长。锂刺激的增殖受到细胞毒性的限制，细胞毒性可以通过在培养基中添加氯化钾（5-20 mM）来调节。锂、17β-雌二醇和 EGF 中的每一种都增加了 MCF-7 细胞对肌醇的摄取率。无论是标准化为肌醇脂质、蛋白质还是DNA，包括锂在内的每种有丝分裂原都会升高肌醇磷酸盐的稳态水平，锂会抑制磷酸肌醇信号通路中肌醇磷酸盐的分解。这些数据表明，治疗浓度的锂可以通过可能涉及磷酸肌醇途径的机制刺激人类乳腺癌细胞的增殖。 (C) 1995 Wiley-Liss, Inc.
Lithium, which is used to treat bipolar psychiatric disorders, can stimulate proliferation of a number of cells in tissue culture. Proliferation of MCF-7 human breast cancer cells, which also respond to EGF and estrogens, was stimulated by LiCl (1-5 mM) within the concentration range that is encountered during human therapy with lithium. Stimulation of growth was specific for lithium; rubidium, potassium, and sodium showed no such effect. In the presence of antiestrogen, lithium stimulated the growth of hormone-dependent breast cancer cells MCF-7, ZR-75-1, and T47D but not hormone-independent MDA-MB-231 cells or an estrogen-independent clone of MCF-7 cells. Lithium-stimulated proliferation was limited by cytotoxicity which could be moderated by added potassium chloride (5-20 mM) in the medium. Each of the mitogens lithium, 17 beta-estradiol, and EGF increased the rate of uptake of myo-inositol into MCF-7 cells. Whether normalized to inositol lipids, to protein, or to DNA, steady-state levels of inositol phosphates were elevated by each of the mitogens including lithium, which inhibits the breakdown of inositol phosphates in the phosphoinositide signaling pathway. These data indicate that therapeutic concentrations of lithium can stimulate the proliferation of human breast cancer cells by a mechanism that may involve the phosphoinositide pathway. (C) 1995 Wiley-Liss, Inc.