Ovarian cancer (OC) represents a collection of rare but lethal gynecologic cancers where the difficulty of early detection due to an often-subtle range of abdominal symptoms contributes to high fatality rates. With the exception of BRCA1/2 mutation carriers, OC most often manifests as a post-menopausal disease, a time in which the ovaries regress and circulating reproductive hormones diminish. Progesterone is thought to be a "protective" hormone that counters the proliferative actions of estrogen, as can be observed in the uterus or breast. Like other steroid hormone receptor family members, the transcriptional activity of the nuclear progesterone receptor (nPR) may be ligand dependent or independent and is fully integrated with other ubiquitous cell signaling pathways often altered in cancers. Emerging evidence in OC models challenges the singular protective role of progesterone/nPR. Herein, we integrate the historical perspective of progesterone on OC development and progression with exciting new research findings and critical interpretations to help paint a broader picture of the role of progesterone and nPR signaling in OC. We hope to alleviate some of the controversy around the role of progesterone and give insight into the importance of nPR actions in disease progression. A new perspective on the role of progesterone and nPR signaling integration will raise awareness to the complexity of nPRs and nPR-driven gene regulation in OC, help to reveal novel biomarkers, and lend critical knowledge for the development of better therapeutic strategies.

中文翻译：

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重新评估黄体酮在卵巢癌中的作用：黄体酮总是具有保护作用吗？


卵巢癌 （OC） 是一系列罕见但致命的妇科癌症，其中由于通常细微的腹部症状范围而难以早期发现，导致高死亡率。除了 BRCA1/2 突变携带者外，OC 最常表现为绝经后疾病，此时卵巢退化和循环生殖激素减少。黄体酮被认为是一种“保护性”激素，可以对抗雌激素的增殖作用，这可以在子宫或乳房中观察到。与其他类固醇激素受体家族成员一样，核孕激素受体 （nPR） 的转录活性可能是配体依赖性或独立性的，并且与癌症中经常改变的其他普遍存在的细胞信号通路完全整合。OC 模型中的新证据挑战了孕酮/nPR 的唯一保护作用。在本文中，我们将孕酮对 OC 发展和进展的历史观点与令人兴奋的新研究结果和批判性解释相结合，以帮助更广泛地描绘孕酮和 nPR 信号在 OC 中的作用。我们希望缓解围绕黄体酮作用的一些争议，并深入了解 nPR 作用在疾病进展中的重要性。关于孕激素和 nPR 信号传导整合作用的新观点将提高对 OC 中 nPR 和 nPR 驱动基因调控复杂性的认识，有助于揭示新的生物标志物，并为开发更好的治疗策略提供关键知识。