Hawkins R A, Scott K M, Freedman B
J Endocrinol. 1983 Jul;98(1):91-102. doi: 10.1677/joe.0.0980091.
Forty-eight rat mammary tumours and 25 human breast carcinomata were examined for (a) oestrogen receptor activity and (b) capacity for intranuclear translocation of oestrogen. Receptor activity was determined by saturation analysis using charcoal adsorption to separate free and bound hormone. The capacity for intranuclear translocation was determined by incubation of tumour slices in Krebs-Ringer bicarbonate solution containing [3H]oestradiol-17 beta at a physiological concentration, in the presence and absence of a large excess of non-radioactive oestradiol, at 37 degrees C. Saturable nuclear uptake of [3H]oestradiol (= translocation) in boiled or receptor-negative tissues was minimal, i.e. less than 12 fmol/mg DNA per 2 h and in receptor-positive tissue was reduced by 85% when the temperature was lowered to 0 degree C. In 27 ovary-independent transplantable tumours and 21 dimethylbenz(a)anthracene-induced tumours (predominantly ovary dependent) saturable nuclear uptake was strongly correlated with level of oestrogen receptor activity (Spearman's rank correlation coefficient r = +0.73, P less than 0.001). Nineteen of these 48 tumours were examined further: 60-80% of the saturable uptake was precipitable with protamine sulphate and this fraction of the total saturable uptake was also highly correlated with receptor level (Spearman's r = +0.87, P less than 0.001). In the 25 human tumours studied, saturable nuclear uptake was again correlated with receptor level (Spearman's r = +0.75, P less than 0.001). These studies suggest that saturable transfer of oestradiol from the extracellular medium through the cytoplasm to the cell nucleus is mediated by the oestrogen receptor in the rat and human tumours examined. They provide no evidence for any defect of the receptor mechanism before nuclear binding in tumours which are receptor positive but hormone insensitive.
对48个大鼠乳腺肿瘤和25个人类乳腺癌进行了以下检查：(a)雌激素受体活性；(b)雌激素的核内转运能力。通过使用活性炭吸附分离游离和结合激素的饱和分析来测定受体活性。通过在37℃下，在含有生理浓度的[3H]雌二醇-17β的Krebs-Ringer碳酸氢盐溶液中孵育肿瘤切片来测定核内转运能力，有无大量过量的非放射性雌二醇存在。在煮沸的或受体阴性的组织中，[3H]雌二醇的可饱和核摄取（即转运）极少，即每2小时每毫克DNA少于12 fmol，当温度降至0℃时，受体阳性组织中的摄取减少85%。在27个不依赖卵巢的可移植肿瘤和21个二甲基苯并(a)蒽诱导的肿瘤（主要依赖卵巢）中，可饱和核摄取与雌激素受体活性水平密切相关（Spearman等级相关系数r = +0.73，P < 0.001）。对这48个肿瘤中的19个进行了进一步检查：60 - 80%的可饱和摄取可被硫酸鱼精蛋白沉淀，并且总可饱和摄取的这一部分也与受体水平高度相关（Spearman's r = +0.87，P < 0.001）。在研究的25个人类肿瘤中，可饱和核摄取再次与受体水平相关（Spearman's r = +0.75，P < 0.001）。这些研究表明，在所检查的大鼠和人类肿瘤中，雌二醇从细胞外介质通过细胞质到细胞核的可饱和转运是由雌激素受体介导的。它们没有提供证据表明在受体阳性但激素不敏感的肿瘤中，在核结合之前受体机制存在任何缺陷。
