Identification of a novel estrogen receptor β1 binding partner, inhibitor of differentiation-1, and role of ERβ1 in human breast cancer cells

Estrogen plays an important role in the proliferation and progression of breast cancer. The estrogen signal is mediated by the estrogen receptors (ERα and ERβ). ERα (estrogen receptor α) is an important promoter of growth in breast cancer; however, the role of ERβ (estrogen receptor β) in breast cancer is less clear. In this study, using a yeast two-hybrid screening technique, we identified a novel ERβ1-interacting protein, inhibitor of differentiation-1 (Id1), which is a dominant negative regulator of bHLH transcription factors, and promotes cell proliferation in breast cancer cells. Using mammalian two-hybrid protein–protein interaction assays, we found that the helix–loop–helix domain of the Id1 protein was essential for the physical interaction between ERβ1 and Id1. In addition, we found that 17-β estradiol inhibits ERβ1 binding with Id1. Furthermore, we observed that ERβ1 inhibited cell growth of MDA-MB-231 cells and upregulated p21 expression and that ERβ1 up-regulation of p21 is Id1 dependent. Taken together, our study demonstrates a novel ERβ1 binding partner, Id1, and a mechanism by which ERβ1 inhibits breast cancer cell growth through binding with Id1 and upregulating p21 gene expression.