Sex steroid receptors expression and hormone-induced cell proliferation in human osteosarcoma
Sex steroid receptors expression and hormone-induced cell proliferation in human osteosarcoma
复制标题
DOI：
10.1111/j.1349-7006.2007.00673.x
复制
发表时间：
2008-03-01
期刊：
影响因子：
5.7
通讯作者：
Sasano, Hironobu
中科院分区：
文献类型：
--
作者：
Dohi, Osamu;Hatori, Masahito;Sasano, Hironobu
性类固醇受体包括雌激素受体（ER）、孕激素受体（PR）和雄激素受体（AR）在人骨肉瘤或其细胞系中偶有报道。因此，性类固醇被认为在人骨肉瘤中发挥了一定的作用，但尚未有关于这些受体在肉瘤细胞中的状态与临床病理参数之间的相关性的系统和详细的研究报道。我们用免疫组化方法检测了28例骨肉瘤中ER、PR和AR的存在。然后，我们利用表达所有这些受体的MG-63人骨肉瘤细胞系，表征了性类固醇对骨肉瘤细胞增殖的潜在影响。绝大多数病例（分别为23例和24例）检测到er - β和PR，但er - α和芳香化酶未在所有病例中检测到，AR仅在8例中检测到。er - β与Ki-67 （MIB1）标记指标呈显著正相关。肿瘤中芳香化酶的缺失也表明循环性类固醇浓度的相对重要性。雌二醇、孕酮和5 α -二氢睾酮（DHT）显著刺激MG-63细胞的增殖，氟维司汀（ICI）、米非司酮（RU）和氢西氟他胺（ER、PR和AR阻滞剂）分别显著抑制MG-63细胞的增殖。性类固醇，特别是雌激素和孕激素，被认为在调节人骨肉瘤细胞增殖中起重要作用。此外，这些数据表明，使用临床可用的黄体酮和雌激素抑制剂治疗骨肉瘤具有新的内分泌治疗潜力。
Sex steroid receptors including estrogen receptors (ER), progesterone receptors (PR), and androgen receptors (AR) have been sporadically reported in human osteosarcoma or its cell lines. Therefore, sex steroids have been considered to play some roles in human osteosarcoma, but no systematic and detailed studies regarding the correlation between the status of these receptors in sarcoma cells and clinicopathological parameters have been reported. We examined the existence of ER, PR and AR in 28 cases of osteosarcoma using immunohistochemistry. We then characterized the potential influence of sex steroids on cell proliferation of osteosarcoma cells using MG-63 human osteosarcoma cell line, which expressed all of these receptors. ER-beta and PR were detected in the great majority of the cases (23 and 24 cases, respectively) but ER-alpha and aromatase were not detected in all the cases, and AR was detected only in eight cases. There was a significant positive correlation between ER-beta and Ki-67 (MIB1) labeling indexes. The absence of aromatase in tumors also suggests the relative importance of concentrations of circulating sex steroids. Proliferation of MG-63 cells was significantly stimulated by estradiol, progesterone, and 5 alpha-dihydrotestosterone (DHT), and was significantly suppressed by the addition of fulvestrant (ICI), mifepristone (RU), and hydroxiflutamide, blockers for ER, PR and AR, respectively. Sex steroids, particularly estrogen and progesterone, are considered to play important roles in the regulation of cell proliferation in human osteosarcoma. In addition, these data suggest the potential for a novel endocrine therapy in osteosarcoma using clinically available inhibitors of progesterone and estrogen actions.