DEC1 directly interacts with estrogen receptor (ER) to suppress proliferation of ER-positive breast cancer cells

Aberrant ER alpha signaling and altered circadian rhythms are both features of ER-positive breast cancer, however, the molecular interaction between them is still not fully understood. Herein, we analyzed the interplay between the circadian rhythm molecule DEC1 and ER alpha and its effect on the proliferation of ER-positive breast cancer cells, providing a new clue for clarifying the pathogenesis of breast cancer. In this study, we revealed that DEC1 negatively regulates the proliferation of ER-positive breast cancer MCF7 cells through interaction with ER alpha protein. DEC1 co-localized with ER alpha in the nucleus of MCF7 cells, stabilized ER alpha protein independently of its transcriptional activity and without affecting by estrogen stimulation and inhibited the degradation of ER alpha mediated by CHX in a time-dependent manner. Moreover, results from luciferase reporter assay showed that overexpression of DEC1 significantly inhibits ERa-mediated transcriptional activity in a dose-dependent manner. These results together suggested that DEC1 may serve as a co-repressor of ER alpha in ER-positive breast cancer. Although DEC1 improved the stability of ER alpha and alleviated protein degradation, DEC1 inhibited the proliferation of MCF7 cells by decreasing ER alpha-mediated signal transduction. (C) 2020 Elsevier Inc. All rights reserved.