卵巢荷爾蒙雌激素和孕酮從青春期到絕經(jīng)都參與乳腺中一系列復(fù)雜的相互作用,。這些變化很多都與細(xì)胞增殖相關(guān)，而且當(dāng)發(fā)生錯誤時乳腺癌便會出現(xiàn),。本期Nature上的兩項(xiàng)研究分析雌激素和孕酮對小鼠乳腺干細(xì)胞(MaSC)功能的影響,。
它們發(fā)現(xiàn)，當(dāng)兩種荷爾蒙在因卵巢切除或藥物阻斷而缺失時MaSC數(shù)量會減少,，但在用雌激素和孕酮治療后其數(shù)量則會增加,。另外，兩個研究小組都發(fā)現(xiàn)RANKL（孕酮的一個目標(biāo),，已知參與骨頭重塑和乳腺形成）在MaSC對孕酮的反應(yīng)中是一個中間物,。(生物谷Bioon.com)
生物谷推薦原文出處：
Nature doi:10.1038/nature09027
Control of mammary stem cell function by steroid hormone signalling
Marie-Liesse Asselin-Labat,Fran?ois Vaillant,Julie M. Sheridan,Bhupinder Pal,Di Wu,Evan R. Simpson,Hisataka Yasuda,Gordon K. Smyth,T. John Martin,Geoffrey J. Lindeman& Jane E. Visvader
The ovarian hormones oestrogen and progesterone profoundly influence breast cancer risk1, 2, 3, underpinning the benefit of endocrine therapies in the treatment of breast cancer4. Modulation of their effects through ovarian ablation or chemoprevention strategies also significantly decreases breast cancer incidence5, 6. Conversely, there is an increased risk of breast cancer associated with pregnancy in the short term7. The cellular mechanisms underlying these observations, however, are poorly defined. Here we demonstrate that mouse mammary stem cells (MaSCs)8, 9 are highly responsive to steroid hormone signalling, despite lacking the oestrogen and progesterone receptors10. Ovariectomy markedly diminished MaSC number and outgrowth potential in vivo, whereas MaSC activity increased in mice treated with oestrogen plus progesterone. Notably, even three weeks of treatment with the aromatase inhibitor letrozole was sufficient to reduce the MaSC pool. In contrast, pregnancy led to a transient 11-fold increase in MaSC numbers, probably mediated through paracrine signalling from RANK ligand. The augmented MaSC pool indicates a cellular basis for the short-term increase in breast cancer incidence that accompanies pregnancy. These findings further indicate that breast cancer chemoprevention may be achieved, in part, through suppression of MaSC function.
