Shao Ruijin
Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg 40530, Sweden.
Ecancermedicalscience. 2013 Dec 18;7:381. doi: 10.3332/ecancer.2013.381.
Progesterone therapy is an effective treatment for atypical endometrial hyperplasia and early endometrial carcinoma (EC). However, progesterone resistance is the main obstacle to the success of conservative treatment in women with type I EC and remains a major clinical challenge. Studies indicate that progesterone and progesterone receptors (PRs) play a significant role in both normal and neoplastic endometria. Most EC arises in the epithelial cells of the endometrial glands, and a large body of in vitro evidence suggests that the absence or reduced expression of PR isoform B might result in the failure of progesterone treatment and lead to aberrant PRB-mediated signalling in EC cells. A recently developed in vivo knockout mouse model suggests that enhanced DNA methylation decreases the level of stromal PR isoform A and that this is also a main contributor to progesterone resistance in EC cells. The endometrial stroma within the EC might create a microenvironment that determines how epithelial-derived cancer cells respond to progesterone. This novel study opened a new avenue for research seeking to clarify the mechanisms that regulate the specific PR isoforms that are associated with the stromal cell responses to progesterone and has led to new understanding of both endometrial cell-specific and mechanical contributions of the stroma to EC development.
孕激素疗法是治疗非典型子宫内膜增生和早期子宫内膜癌（EC）的有效方法。然而，孕激素抵抗是I型EC女性保守治疗成功的主要障碍，仍然是一个重大的临床挑战。研究表明，孕激素和孕激素受体（PRs）在正常和肿瘤性子宫内膜中均发挥重要作用。大多数EC发生于子宫内膜腺体的上皮细胞，大量体外证据表明，PR异构体B的缺失或表达降低可能导致孕激素治疗失败，并导致EC细胞中PRB介导的信号异常。最近建立的体内基因敲除小鼠模型表明，DNA甲基化增强会降低基质PR异构体A的水平，这也是EC细胞孕激素抵抗的主要原因。EC内的子宫内膜基质可能会创造一个微环境，决定上皮来源的癌细胞对孕激素的反应。这项新研究为旨在阐明调节与基质细胞对孕激素反应相关的特定PR异构体的机制的研究开辟了一条新途径，并使人们对基质对EC发展的子宫内膜细胞特异性和机械性贡献有了新的认识。
