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

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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.