生物谷Bioon.com 讯 香港玛嘉烈医院的癌症研究人员发现，卵巢激素孕酮在改变乳腺干细胞方面承担了重要的角色，这项发现对乳腺癌的患病风险研究具有重要意义。
专题：Nature系列
这项研究具有重要意义，因为生殖历史（reproductive history）是乳腺癌最强的风险因子，其他已知的主要影响因子还有年龄，遗传因子和乳腺密度等。该研究是由分子生物学家Rama Khokha负责的，研究结果发布在最新一期Nature的在线版本上
文章作者Purna Joshi表示，这项研究能够解释乳腺干细胞在自然生殖过程中如何以及何时会受荷尔蒙影响。研究表明，在月经的下半个周期孕酮分泌会达到峰值，此时干细胞和邻近细胞开始相互交流，驱使正常的乳腺干细胞数量扩增，这就可能导致环境改变使得癌症易于发生。
直到现在，普遍观点认为在成年女性乳房中，乳腺干细胞一般是不活跃的， Khokha博士介绍说，在这项研究中，研究人员通过在小鼠中复制人类自然的生殖周期确定荷尔蒙对乳腺干细胞的影响。
这项关于荷尔蒙改变乳腺干细胞的研究为乳腺癌初期的细胞生长开启了新的理解方式，有利于开发新的干细胞靶向定位方法。
这是第一个关于孕酮驱使乳腺干细胞发生动态变化的证据，这种激活机制为细胞变化过程的开启提供了机会，并最终导致乳腺癌的发生。
这项研究是由加拿大癌症研究协会和加拿大乳癌基金支持的。（生 物 谷Bioon.com）
更多阅读
CCR：西兰花富含抗乳腺癌物质可杀死乳腺癌干细胞
Nature Genetics：乳腺癌和卵巢癌易感基因RAD51C
Cell：组蛋白去甲基化酶LSD1可影响乳腺癌转移
Cell Stem Cell：Notch信号调节乳腺干细胞
Nature：歼灭致癌干细胞 根治癌症新突破
生物谷推荐原文出处：
Nature doi:10.1038/nature09091
Progesterone induces adult mammary stem cell expansion
Purna A. Joshi1, Hartland W. Jackson1, Alexander G. Beristain1, Marco A. Di Grappa1, Patricia Mote2, Christine Clarke2, John Stingl3, Paul D. Waterhouse1 & Rama Khokha1
Reproductive history is the strongest risk factor for breast cancer after age, genetics and breast density1, 2. Increased breast cancer risk is entwined with a greater number of ovarian hormone-dependent reproductive cycles, yet the basis for this predisposition is unknown3, 4, 5. Mammary stem cells (MaSCs) are located within a specialized niche in the basal epithelial compartment that is under local and systemic regulation6. The emerging role of MaSCs in cancer initiation warrants the study of ovarian hormones in MaSC homeostasis. Here we show that the MaSC pool increases 14-fold during maximal progesterone levels at the luteal dioestrus phase of the mouse. Stem-cell-enriched CD49fhi cells amplify at dioestrus, or with exogenous progesterone, demonstrating a key role for progesterone in propelling this expansion. In aged mice, CD49fhi cells display stasis upon cessation of the reproductive cycle. Progesterone drives a series of events where luminal cells probably provide Wnt4 and RANKL signals to basal cells which in turn respond by upregulating their cognate receptors, transcriptional targets and cell cycle markers. Our findings uncover a dynamic role for progesterone in activating adult MaSCs within the mammary stem cell niche during the reproductive cycle, where MaSCs are putative targets for cell transformation events leading to breast cancer.
1 Ontario Cancer Institute, Department of Medical Biophysics and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5G 2M9, Ontario, Canada
2 Department of Medicine, Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead, New South Wales 2145, Australia
3 Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge CB2 0RE, UK
