Proliferation of breast cancer stem cells via NO/cGMP signaling pathway

越来越多的证据表明，乳腺癌的发展起源于癌症干细胞，可以通过基于醛脱氢酶（ALDH）活性的流式细胞术分析分离出来。然而，癌症干细胞的生长调控尚未完全了解。在本研究中，我们发现雌激素增加了MCF-7细胞中aldh阳性细胞群的大小。雌激素受体（ER）拮抗剂ICI182780可抑制雌激素的作用。接下来我们检查了ER的下游通路。选择性NOS抑制剂抑制雌激素对NO生成和aldh阳性细胞群大小的影响。8-Br-cGMP还能模拟雌激素的作用。综上所述，这些数据表明雌激素通过NO/cGMP信号通路扩张乳腺癌干细胞。

Growing evidence suggests that development of breast cancer is originated from cancer stem cells, which can be isolated by aldehyde dehydrogenase (ALDH) activity-based flow cytometry analysis. However, the growth regulation of cancer stem cells has not been fully understood. In the present study, we found that estrogen increased the size of ALDH-positive cell population in MCF-7 cells. The effect of estrogen was inhibited by the estrogen receptor (ER) antagonist ICI182780. We next examined the downstream pathway from the ER. A selective NOS inhibitor inhibited the effect of estrogen on NO production and the size of ALDH-positive cell population. In addition, 8-Br-cGMP mimicked the effect of estrogen. Taken together, these data suggest the estrogen expands breast cancer stem cells through the NO/cGMP signaling pathway.