Identification Of Estrogen Receptor β Binding Partner, And Biological Significance Of ERβ-Id1 Interaction In Breast Cancer

Incidence of breast cancer has been on rise in recent 20 years. Breast cancer is a kind of estrogen-depentent carcinoma. It is recognized that cell signals between estrogen and estrogen receptors play an important role in carcinogenesis of breast cancer. There are two kinds of estrogen receptors, Erαand ERβ. Previous studies show that ERβ1 is tumor suppressor gene and its biological role is still unknown.Objective We identified a novel binding partner of ERβby using a yeast two-hybrid screening technique and investigate the biological role of ERβin breast cancer. Methods In first part, we used LBD domain of ERβ1 as a bait to screen the binding partner of ERβ1by using a yeast two-hybrid screening technique. In second part, we identified specific domain of Id1 by using mammalian two-hybrid protein-protein interaction assays.In third part, we investigated effect of ERβ1- Id1 interation and its biological significance in breast cancer by using RNA interference,reporter gene assays and other techniques.Results By using a yeast two-hybrid screening technique, we found Id1 was ERβ1 interacting protein. By using mammalian two-hybrid protein-protein interaction assays, we found helix-loop-helix domain of Id1 was responsible for the physical interaction between ERβ1and Id1. In addition, we found that estradiol inhibited ERβ1 binding with Id1. Furthermore, we observed that ERβ1 inhibited cell growth of MDA-MB-231 cells and it could upregulate p21 expression and that ERβ1 upregulation of p21 was Id1 dependent.Conclusion Id1 is a novel interacting protein of ERβ1. HLH domain is essential for the interaction between ERβ1 and Id1. 17β-estradiol inhibits ERβ1 binding with Id1. Id1 could promote cell proliferation while ERβ1 inhibits cell growth. ERβ1 could inhibit cell growth of breast cancer cell line MDA-MB-231 by upregulating p21 expression.