Shao Ruyue, Fang Liaoqiong, Xing Ruoxi, Xiong Yu, Fang Liaoqiong, Wang Zhibiao
State Key Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing and The Ministry of Science and Technology, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, PR China.
Institute of Life Science, Chongqing Medical University, Chongqing 400016, PR China.
Biochem Biophys Res Commun. 2015;468(1-2):136-42. doi: 10.1016/j.bbrc.2015.10.145. Epub 2015 Oct 31.
Uterine leiomyomas are benign myometrial neoplasms that function as one of the common indications for hysterectomy. Clinical and biological evidences indicate that uterine leiomyomas are estrogen-dependent. Estrogen stimulates cell proliferation through binding to the estrogen receptor (ER), of which both subtypes α and β are present in leiomyomas. Clinically, leiomyomas may be singular or multiple, where the first one is rarely recurring if removed and the latter associated to a relatively young age or genetic predisposition. These markedly different clinical phenotypes indicate that there may different mechanism causing a similar smooth muscle response. To investigate the relative expression of ERα and ERβ in multiple and solitary uterine leiomyomas, we collected samples from 35 Chinese women (multiple leiomyomas n = 20, solitary leiomyoma n = 15) undergoing surgery to remove uterine leiomyomas. ELISA assay was performed to detect estrogen(E2) concentration. Quantitative real-time PCR analysis was performed to detect ERα and ERβ mRNA expression. Western blot and immunohistochemical analysis were performed to detect ERα and ERβ protein expression. We found that ERα mRNA and protein levels of in multiple leiomyomas were significantly lower than those of solitary leiomyomas, whereas ERβ mRNA and protein levels in multiple leiomyomas were significantly higher than those in solitary leiomyomas, irrespectively of the menstrual cycle stage. In both multiple and solitary leiomyomas, ERα expression was higher than that of ERβ. E2 concentration in multiple and solitary leiomyomas correlated with that of ERα expression. ERα was present in nuclus and cytoplasma while estrogen receptor β localized only in nuclei in both multiple and solitary leiomyomas. Our findings suggest that the difference of ERα and ERβ expression between multiple and solitary leiomyomas may be responsible for the course of the disease subtypes.
子宫平滑肌瘤是良性子宫肌层肿瘤，是子宫切除术的常见指征之一。临床和生物学证据表明，子宫平滑肌瘤依赖雌激素。雌激素通过与雌激素受体（ER）结合来刺激细胞增殖，子宫平滑肌瘤中同时存在α和β两种亚型的雌激素受体。临床上，平滑肌瘤可以是单发或多发，其中单发肌瘤切除后很少复发，而多发肌瘤则与相对年轻的年龄或遗传易感性有关。这些明显不同的临床表型表明，可能存在不同的机制导致相似的平滑肌反应。为了研究ERα和ERβ在多发和单发子宫平滑肌瘤中的相对表达，我们收集了35名接受子宫平滑肌瘤切除术的中国女性的样本（多发肌瘤n = 20，单发肌瘤n = 15）。采用ELISA法检测雌激素（E2）浓度。采用定量实时PCR分析检测ERα和ERβ mRNA表达。采用蛋白质免疫印迹和免疫组织化学分析检测ERα和ERβ蛋白表达。我们发现，无论月经周期处于何阶段，多发肌瘤中ERα mRNA和蛋白水平均显著低于单发肌瘤，而多发肌瘤中ERβ mRNA和蛋白水平均显著高于单发肌瘤。在多发和单发肌瘤中，ERα的表达均高于ERβ。多发和单发肌瘤中的E2浓度与ERα表达相关。在多发和单发肌瘤中，ERα存在于细胞核和细胞质中，而雌激素受体β仅定位于细胞核中。我们的研究结果表明，多发和单发平滑肌瘤中ERα和ERβ表达的差异可能是导致疾病亚型病程不同的原因。
