文摘
Accumulating evidence supports the theory that breast cancer arises from a subpopulation of mammary stem/progenitor cell which posses the ability to self-renew. However, the involvement of estrogen signaling in regulation of breast cancer stem/progenitor cells has not been fully established, mainly because expression and function of ER-¦Á in breast cancer stem cells remains controversial. Previously, our laboratory cloned a variant of ER-¦Á, ER-¦Á36, and found that ER-¦Á36-mediated non-genomic estrogen signaling plays an important role in malignant growth of triple-negative breast cancer cells. In this study, we found that ER-¦Á36 was highly expressed in ER-negative breast cancer SK-BR-3 cells and mediated non-genomic estrogen signaling such as activation of the MAPK/ERK signaling in these cells. Knock-down of ER-¦Á36 expression in these cells using the shRNA method diminished their responsiveness to estrogen and significantly down-regulated HER2 expression. HER2 signaling activated ER-¦Á36 transcription through an AP1 site in the ER-¦Á36 promoter and ER-¦Á36 physically interacted with HER2. We also found that ER-¦Á36 is highly expressed in a subset of SK-BR-3 cells that was positive for ALDH1, a breast cancer stem cell marker, and knock-down of ER-¦Á36 expression reduced the population of ALDH1 positive cells. Our results thus demonstrated that ER-¦Á36 positively regulates HER2 expression and the population of ALDH1 positive breast cancer cells, and suggested that non-genomic estrogen signaling mediated by ER-¦Á36 is involved in maintenance and regulation of breast cancer stem cells.
