Abstract
Androgen receptor (AR) is an important transcriptional factor, which is frequently expressed in invasive breast cancer and correlates patients' prognosis. Our previous results indicate AR activation may increase let-7a expression in breast cancer cells, while let-7, a tumor suppressor, is reported to inhibit breast tumor-initiating cells (T-IC). The study aims to explore the effects of AR/let-7a signaling on breast T-IC and its regulatory mechanism. The results revealed that the expression of AR was significantly associated with let-7a and CD44+/24-/low especially in estrogen receptor positive (ER+) breast cancer tissues. The expression of AR and let-7a indicated better outcome, while patients with CD44+/24-/low phenotype had worse prognosis. AR activation induced by dihydrotestosterone (DHT) prevented cells proliferation, migration, invasion and self-renewal capacities in ER+ breast cancer cells, via transcriptional up-regulation of let-7a. In addition, AR could inhibit tumorigenesis and metastasis of ER+ breast cancer cells in the serial xenotranplanted animal models. Our data suggested that AR/let-7a signaling could inhibit the biological behavior of tumor-initiating cells (T-IC) in ER+AR+ breast cancers, which might become a new therapeutic target.