用在避孕藥和荷爾蒙替代療法中的孕酮已被與乳腺癌聯(lián)系起來(lái)。現(xiàn)在,，獨(dú)立工作的兩個(gè)小組發(fā)現(xiàn)了這種聯(lián)系的一個(gè)機(jī)制基礎(chǔ)。
Schramek等人在一個(gè)小鼠模型中發(fā)現(xiàn),，合成孕酮可以通過(guò)誘導(dǎo)破骨細(xì)胞分化因子RANKL（該因子通過(guò)RANKL受體RANK作用在乳房上皮細(xì)胞上）來(lái)促進(jìn)乳腺腫瘤形成,。
Gonzalez-Suarez等人發(fā)現(xiàn)，RANKL的抑制可以降低荷爾蒙誘導(dǎo)的以及其他小鼠乳腺腫瘤模型中的腫瘤發(fā)生,，從而提出一種新的治療方法,。一種RANKL抑制因子(denosumab)正在進(jìn)行臨床試驗(yàn)，將其作為絕經(jīng)后骨質(zhì)疏松癥中骨頭丟失的一種治療方法,，同時(shí)也用它來(lái)治療轉(zhuǎn)移性骨病中與骨骼相關(guān)的癥狀,。（生物谷Bioon.com）
生物谷推薦英文摘要：
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.
