The correlation between autophagy and tamoxifen resistance in breast cancer.

Abstract

Tamoxifen is recommended as a first line treatment for estrogen receptor positive breast cancer. However, the acquisition of endocrine resistance remains the biggest hurdle to achieving treatment success. We, therefore, designed the present study to disclose the relationship between autophagy and endocrine resistance and to provide some insight into overcoming tamoxifen resistance. Experiments were performed using TAM-sensitive (MCF-7) cell lines and TAM-resistant (TAM-R) cell lines. Western blot, real-time PCR, and immunofluorescence analyses were conducted to detect autophagy and apoptosis related proteins and to evaluate pathways that stimulated autophagy in the two targeted cell lines. Higher LC3 and Beclin-1 levels were found in the TAM-R cell lines compared with the MCF-7 cell lines, suggesting that the degree of autophagy was higher in the TAM-R cells. Other proteins kinases such as pAMPK, BAX, and p-p70S6K also proved the involvement of autophagy in the process of developing tamoxifen resistance. Lower levels of microRNA-101 were detected in the TAM-R cells, indicating a negative correlation between microRNA-101 and autophagy. Based on the findings presented in this study, autophagy is a major cause of tamoxifen resistance in breast cancer patients. Inhibiting autophagy could improve the therapeutic efficacy of TAM by overcoming endocrine resistance in estrogen receptor positive breast cancers.