A putative human breast stem cell population is enriched for steroid receptor-positive cells
A putative human breast stem cell population is enriched for steroid receptor-positive cells
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DOI：
10.1016/j.ydbio.2004.07.044
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发表时间：
2005-01-15
影响因子：
2.7
通讯作者：
Potten, CS
中科院分区：
文献类型：
--
作者：
Clarke, RB;Spence, K;Potten, CS
乳腺上皮干细胞被认为是乳腺癌病因学的主要靶点。由于乳腺癌主要表达雌激素和孕激素受体（er α和PR），我们研究了这些er α /PR阳性细胞的生物学特性及其与正常人乳腺上皮干细胞的关系。我们采用了几种互补的方法来鉴定假定的干细胞标记物，以表征分离的干细胞群体，并将这些细胞与表达类固醇受体er - α和PR的细胞联系起来。通过将人类组织植入胸腺裸小鼠中进行DNA放射性标记，证明了一群保留标记的细胞富含假定的干细胞标记物p21（CIP1）和Msi-1，这是Musashi果蝇的人类同源物。类固醇受体阳性细胞与细胞角蛋白19（乳腺中另一种假定的干细胞标记物）共表达这些干细胞标记物。由于缺乏肌上皮和管腔顶膜标记物的表达，人类乳腺上皮细胞具有乳腺干细胞特有的Hoechst染料外排“侧群”（SP）特性，被证明是未分化的“中间”细胞。与非SP细胞相比，这些SP细胞中erα阳性细胞的含量增加了6倍，erα、p21（CIP1）和Msi1基因的表达量增加了数倍。与非SP细胞相比，SP细胞在基质中形成分支结构，包括管腔细胞和肌上皮细胞。这些数据表明，在一个模型中，分散的类固醇受体阳性细胞是通过不对称细胞分裂自我更新的干细胞，并产生转运扩增和分化细胞的斑块。(C) 2004爱思唯尔公司版权所有。
Breast epithelial stem cells are thought to be the primary targets in the etiology of breast cancer. Since breast cancers, mostly express estrogen and progesterone receptor (ERalpha and PR), we examined the biology of these ERalpha/PR-positive cells and their relationship to stem cells in normal human breast epithelium. We employed several complementary approaches to identify putative stem cell markers, to characterise an isolated stem cell population and to relate these to cells expressing the steroid receptors ERalpha and PR. Using DNA radiolabelling in human tissue implanted into athymic nude mice, a population of label-retaining cells were shown to be enriched for the putative stem cell markers p21(CIP1) and Msi-1, the human homolog of Drosophila Musashi. Steroid receptor-positive cells were found in co-express these stem cell markers together with cytokeratin 19, another putative stem cell marker in the breast. Human breast epithelial cells with Hoechst dye-effluxing "side population" (SP) properties characteristic of mammary stem cells in truce were demonstrated to be undifferentiated "intermediate" cells by lack of expression of myoepithelial and luminal apical membrane markers. These SP cells were 6-fold enriched for ERalpha-positive cells and expressed several fold higher levels of the ERalpha, p21(CIP1) and Msi1 genes than non-SP cells. In contrast to non-SP cells, SP cells formed branching structures in matrigel which included cells of both luminal and myoepithelial lineages. The data suggest a model where scattered steroid receptor-positive cells are stem cells that self-renew through asymmetric cell division and generate patches of transit amplifying and differentiated cells. (C) 2004 Elsevier Inc. All rights reserved.