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有读书笔记Control of mammary stem cell function by steroid hormone signalling

Dr.LinZhen 添加于 2010-6-11 10:55 | 1195 次阅读 | 1 个评论

  •  作 者

    Asselin-Labat M-L, Vaillant F, Sheridan JM, Pal B, Wu D, Simpson ER, Yasuda H, Smyth GK, Martin TJ, Lindeman GJ, Visvader JE

  •  摘 要

    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.

  •  详细资料

    • 文献种类:期刊
    • 期刊名称: Nature
    • 期刊缩写: Nature
    • 期卷页: 2010年  第465卷 第7299期 798-802页
    • ISBN: 0028-0836

  • 相关链接 DOI URL 

  •  Dr.LinZhen 的文献笔记  订阅

    雌激素和孕酮对MaSC功能的影响

    卵巢荷尔蒙雌激素和孕酮从青春期到绝经都参与乳腺中一系列复杂的相互作用。这些变化很多都与细胞增殖相关，而且当发生错误时乳腺癌便会出现。本期Nature上的两项研究分析雌激素和孕酮对小鼠乳腺干细胞(MaSC)功能的影响。它们发现，当两种荷尔蒙在因卵巢切除或药物阻断而缺失时MaSC数量会减少，但在用雌激素和孕酮治疗后其数量则会增加。另外，两个研究小组都发现RANKL（孕酮的一个目标，已知参与骨头重塑和乳腺形成）在MaSC对孕酮的反应中是一个中间物

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