Let-7: a regulator of the ERα signaling pathway in human breast tumors and breast cancer stem cells.

Abstract

The oncogenic role of estrogen receptor (ER)α and its correlation with let-7 microRNAs (miRNAs) have been studied and confirmed in breast tumors; however, this correlation has not been investigated in breast cancer stem cells (BCSCs). In the present study, we detected the expression of let-7 and ERα in ER-positive breast tumor tissues. Furthermore, we used a FACSAria cell sorter to separate side population (SP) cells from the MCF-7 and T47-D cell lines by Hoechst 33342 staining. The expression of let-7 miRNAs, ERα and its downstream genes in SP and non-SP (NSP) cells were analyzed. In additional experiments, we transfected a plasmid expressing let-7a into SP cells isolated from the MCF-7 and T47-D cell lines in order to observe changes in the expression of downstream genes (cyclin D1 and pS2). The correlation among let-7, ERα and ERα downstream genes suggested that let-7 acts as a tumor suppressor by inhibiting ERα-mediated cellular malignant growth in ER-positive breast cancer stem cells. The suppression of ERα by the upregulation of let-7 expression may be a promising strategy for the inhibition of the ER signaling pathway and for the elimination of cancer stem cells, thus aiding in the treatment of breast cancer.

• Authors: Xin Sun, Sida Qin, Chong Fan, Chongwen Xu, Ning Du, Hong Ren
• Journal: Oncology reports (Oncol Rep) Vol. 29 Issue 5 Pg. 2079-87 (May 2013) ISSN: 1791-2431 [Electronic] Greece
• PMID: 23467929 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Estrogen Receptor alpha
• MicroRNAs
• PSEN2 protein, human
• Presenilin-2
• mirnlet7 microRNA, human
• Cyclin D1

Topics

• Apoptosis (genetics)
• Breast Neoplasms (genetics, metabolism)
• Cell Cycle (genetics)
• Cell Line, Tumor
• Cyclin D1 (genetics, metabolism)
• Estrogen Receptor alpha (genetics, metabolism)
• Female
• Humans
• MCF-7 Cells
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Neoplastic Stem Cells (metabolism)
• Presenilin-2 (genetics, metabolism)
• Side-Population Cells (metabolism)
• Signal Transduction
• Up-Regulation