Aberrant survivin expression in endometrial hyperplasia: another mechanism of progestin resistance
Aberrant survivin expression in endometrial hyperplasia: another mechanism of progestin resistance
复制标题
子宫内膜增生中生存素的异常表达：孕激素抵抗的另一种机制
DOI：
10.1038/modpathol.2009.25
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发表时间：
2009-05-01
期刊：
影响因子：
7.5
通讯作者：
Zheng, Wenxin
中科院分区：
文献类型：
--
作者：
Chen, Xiaojun;Zhang, Zhenbo;Zheng, Wenxin
在接受孕激素治疗的子宫内膜增生症患者中，高达30%的失败率促使人们更详细地了解孕激素抵抗的机制。Survivin是抗细胞凋亡网络中的关键调节因子，已有研究发现Survivin在子宫内膜增生症和肿瘤中过表达。本研究探讨Survivin在子宫内膜增生症孕激素抵抗中的作用。对23名妇女治疗前后的子宫内膜增生症组织样本进行检测，以了解与孕激素治疗相关的Survivin表达的变化。免疫印迹法检测连续和间歇性孕激素对Ishikawa细胞Survivin表达的影响。所有孕激素治疗前子宫内膜增生症标本的上皮室均有Survivin免疫反应，平均核指数为78，胞浆指数为114。在15例孕激素反应者中，Survivin在上皮细胞核中的表达平均降低19.5倍(P<；0.001)，在上皮细胞质中的表达平均降低8倍(P<；0.001)。在8名无反应者中，未检测到Survivin表达的显著变化。在体外培养的Ishikawa细胞中，无论是用10 MU的醋酸甲羟孕酮持续作用72小时，还是停用醋酸甲羟孕酮后72小时，Survivin的表达都能被有效地抑制。我们的结果表明，Survivin在增生性子宫内膜中的表达异常可能是孕激素抵抗的部分分子机制。对于子宫内膜增生症的临床治疗，间歇性的孕激素治疗可能比连续治疗更有效。
Up to 30% of failure rate in endometrial hyperplasia patients treated by progestin urges more detailed understanding of the mechanisms involved in progestin resistance. Survivin is a key regulator in the antiapoptotic network, and overexpression of survivin has been reported in endometrial hyperplasia and cancer. This study investigated the role of survivin in progestin resistance in endometrial hyperplasia. Pre- and post-treatment endometrial hyperplasia tissue samples from 23 women were examined for changes in survivin expression related to the administration of progestins. The impact of continuous or intermittent progestin treatment on survivin expression in Ishikawa cells was examined by the western blot. Survivin immunoreactivity was present in epithelial compartment of all pre-progestin-treated endometrial hyperplasia samples with mean nuclear indices 78 and cytoplasmic indices 114. In the 15 progestin responders, an average of 19.5-fold decrease of survivin expression was seen in epithelial nuclei (P<0.001) and 8-fold decrease in epithelial cytoplasm (P<0.001). In the eight non-responders, no significant changes in survivin expression were detected. With in vitro Ishikawa cells, survivin expression was effectively inhibited by either 72-h continuous treatment with 10 muM medroxyprogesterone acetate or 72 h after medroxyprogesterone acetate withdrawal. Our results indicated that dysregulation of survivin expression in hyperplastic endometrium may be part of the molecular mechanisms for progestin resistance. Intermittent, rather than continuous, progestin treatment may be more effective clinically for the treatment of endometrial hyperplasia.