Control of mammary stem cell function by steroid hormone signalling
butterfly09 添加于 2010-8-22 23:39
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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
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