用在避孕药和荷尔蒙替代疗法中的孕酮已被与乳腺癌联系起来。现在，独立工作的两个小组发现了这种联系的一个机制基础。
Schramek等人在一个小鼠模型中发现，合成孕酮可以通过诱导破骨细胞分化因子RANKL（该因子通过RANKL受体RANK作用在乳房上皮细胞上）来促进乳腺肿瘤形成。
Gonzalez-Suarez等人发现，RANKL的抑制可以降低荷尔蒙诱导的以及其他小鼠乳腺肿瘤模型中的肿瘤发生，从而提出一种新的治疗方法。一种RANKL抑制因子(denosumab)正在进行临床试验，将其作为绝经后骨质疏松症中骨头丢失的一种治疗方法，同时也用它来治疗转移性骨病中与骨骼相关的症状。（生物谷Bioon.com）
生物谷推荐英文摘要：
Nature doi:10.1038/nature09387
Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer
Daniel Schramek,Andreas Leibbrandt,Verena Sigl,Lukas Kenner,John A. Pospisilik,Heather J. Lee,Reiko Hanada,Purna A. Joshi,Antonios Aliprantis,Laurie Glimcher,Manolis Pasparakis,Rama Khokha,Christopher J. Ormandy,Martin Widschwendter,Georg Schett& Josef M. Penninger
Breast cancer is one of the most common cancers in humans and will on average affect up to one in eight women in their lifetime in the United States and Europe1. The Women’s Health Initiative and the Million Women Study have shown that hormone replacement therapy is associated with an increased risk of incident and fatal breast cancer2, 3. In particular, synthetic progesterone derivatives (progestins) such as medroxyprogesterone acetate (MPA), used in millions of women for hormone replacement therapy and contraceptives, markedly increase the risk of developing breast cancer. Here we show that the in vivo administration of MPA triggers massive induction of the key osteoclast differentiation factor RANKL (receptor activator of NF-κB ligand) in mammary-gland epithelial cells. Genetic inactivation of the RANKL receptor RANK in mammary-gland epithelial cells prevents MPA-induced epithelial proliferation, impairs expansion of the CD49fhi stem-cell-enriched population, and sensitizes these cells to DNA-damage-induced cell death. Deletion of RANK from the mammary epithelium results in a markedly decreased incidence and delayed onset of MPA-driven mammary cancer. These data show that the RANKL/RANK system controls the incidence and onset of progestin-driven breast cancer.
