Melatonin increases oestrogen receptor binding activity of human breast cancer cells
Melatonin increases oestrogen receptor binding activity of human breast cancer cells
复制标题
褪黑素增加人乳腺癌细胞雌激素受体结合活性
作者：
D. Danforth;L. Tamarkin;M. Lippman
乳腺癌通常是一种激素依赖的肿瘤，一些研究表明松果体激素褪黑素可能会影响这种恶性肿瘤的生长和发展。皮下注射褪黑激素已被证明可抑制二甲基苯并(A)菲(DMBA)诱导的大鼠乳腺肿瘤的发展，松果体切除可促进其发展。使用精神药物Torazine可以提高血浆褪黑激素水平，这与精神病患者乳腺癌发病率的降低有关。松果体的钙化与女性乳腺癌发病率的增加有关。虽然褪黑素影响这些肿瘤的机制尚不清楚，但人类乳腺癌和DMBA诱导的肿瘤都含有雌激素受体(ER)，并对雌激素环境的变化做出反应。因此，我们想知道褪黑素是否可能改变这些肿瘤的ER结合活性。我们报道了在生理条件下，MCF-7人乳腺癌细胞与褪黑素体外孵育后，在40分钟内胞浆和胞核ER活性增加，而受体的平衡解离常数(Kd)没有变化。这种诱导作用被放线菌亚胺阻断，因此需要持续的蛋白质合成。另一种内源性激素对乳腺癌ER结合活性的调节可能对了解乳腺癌的行为和治疗具有重要意义，并可能为深入了解调节类固醇激素受体的合成和代谢的因素提供依据。
Breast cancer is frequently a hormone-dependent tumour, and several studies have suggested that the pineal gland hormone melatonin may influence the growth and development of this malignancy. Subcutaneous injections of melatonin have been shown to inhibit, and pinealectomy to enhance, the development of dimethyl benz(a)anthracene (DMBA)-induced mammary tumours in rats1. Use of the psychotropic drug thorazine, which increases plasma melatonin levels2, has been associated with a decreased incidence of breast cancer in psychiatric patients3. Calcification of the pineal gland has been correlated with an increased incidence of breast cancer in women4. While the mechanism by which melatonin influences these tumours is unknown, both human breast cancer and DMBA-induced tumours contain oestrogen receptors (ER) and respond to changes in the oestrogen milieu5–7. We therefore wondered whether melatonin might be altering ER binding activity of these tumours. We report here that in vitro incubation of MCF-7 human breast cancer cells with melatonin in physiological conditions increased the cytoplasmic and nuclear ER activity of these cells within 40 min, giving no change in the equilibrium dissociation constant (Kd) of the receptor. This induction was blocked by cycloheximide, and thus requires continuous protein synthesis. The modulation of ER binding activity of breast cancer by another endogenous hormone may be important for understanding the behaviour and treatment of this disease, and may provide insight into the factors regulating the synthesis and metabolism of steroid hormone receptors.
DOI：
--
发表时间：
1980
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Horwitz,KB;McGuire,WL
通讯作者：
McGuire,WL