生物谷Bioon.com 訊 香港瑪嘉烈醫(yī)院的癌癥研究人員發(fā)現(xiàn)，卵巢激素孕酮在改變?nèi)橄俑杉?xì)胞方面承擔(dān)了重要的角色，這項(xiàng)發(fā)現(xiàn)對(duì)乳腺癌的患病風(fēng)險(xiǎn)研究具有重要意義,。
專題：Nature系列
這項(xiàng)研究具有重要意義,，因?yàn)樯硽v史（reproductive history）是乳腺癌最強(qiáng)的風(fēng)險(xiǎn)因子,，其他已知的主要影響因子還有年齡,，遺傳因子和乳腺密度等。該研究是由分子生物學(xué)家Rama Khokha負(fù)責(zé)的,，研究結(jié)果發(fā)布在最新一期Nature的在線版本上
文章作者Purna Joshi表示,，這項(xiàng)研究能夠解釋乳腺干細(xì)胞在自然生殖過程中如何以及何時(shí)會(huì)受荷爾蒙影響。研究表明，在月經(jīng)的下半個(gè)周期孕酮分泌會(huì)達(dá)到峰值,，此時(shí)干細(xì)胞和鄰近細(xì)胞開始相互交流,，驅(qū)使正常的乳腺干細(xì)胞數(shù)量擴(kuò)增，這就可能導(dǎo)致環(huán)境改變使得癌癥易于發(fā)生,。
直到現(xiàn)在,，普遍觀點(diǎn)認(rèn)為在成年女性乳房中，乳腺干細(xì)胞一般是不活躍的,， Khokha博士介紹說,，在這項(xiàng)研究中，研究人員通過在小鼠中復(fù)制人類自然的生殖周期確定荷爾蒙對(duì)乳腺干細(xì)胞的影響,。
這項(xiàng)關(guān)于荷爾蒙改變?nèi)橄俑杉?xì)胞的研究為乳腺癌初期的細(xì)胞生長(zhǎng)開啟了新的理解方式,，有利于開發(fā)新的干細(xì)胞靶向定位方法。
這是第一個(gè)關(guān)于孕酮驅(qū)使乳腺干細(xì)胞發(fā)生動(dòng)態(tài)變化的證據(jù),，這種激活機(jī)制為細(xì)胞變化過程的開啟提供了機(jī)會(huì),，并最終導(dǎo)致乳腺癌的發(fā)生。
這項(xiàng)研究是由加拿大癌癥研究協(xié)會(huì)和加拿大乳癌基金支持的,。（生 物 谷Bioon.com）
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生物谷推薦原文出處：
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
