聯(lián)系電話
上海勁馬實驗設(shè)備有限公司
中級會員·17年
- 聯(lián)系人：
- 馮經(jīng)理
- 電話：
- 021-60521817
- 手機：
- 13817140470
- 售后：
- 86-021-61107441
- 傳真：
- 86－021－64881400
- 地址：
- 上海市松江區(qū)漕河涇研展路455號B座
- 個性化：
- www.shjmsw.com
- 手機站：
- m.shjmsw.com
- 網(wǎng)址：
- www.shjmsw.com
掃一掃訪問手機商鋪
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
上一篇：*抗腫瘤血管藥物獲準進入中國臨床
下一篇：破解DNA中的剪接密碼
