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 (ER alpha and ER beta). ER alpha (estrogen receptor alpha) is an important promoter of growth in breast cancer; however, the role of ER beta (estrogen receptor beta in breast cancer is less clear. In this study, using a yeast two-hybrid screening technique, we identified a novel ER beta 1-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 ER beta 1 and Id1. In addition, we found that 17-beta estradiol inhibits ER beta 1 binding with Id I. Furthermore, we observed that ER beta 1 inhibited cell growth of MDA-MB-231 cells and upregulated p21 expression and that ER beta 1 upregulation of p21 is Id1 dependent. Taken together, our study demonstrates a novel ER beta 1 binding partner, Id1, and a mechanism by which ER beta 1 inhibits breast cancer cell growth through binding with Id1 and upregulating p21 gene expression. (C) 2009 Elsevier Ireland Ltd. All rights reserved.