ESR2 and Familial prostate cancer: Further supporting the necessity of ZFHX3 for ERβ’s tumor suppressor activity, we found that ERβ and ZFHX3 cooperate to repress the transcription of MYC. For example, ERβ physically interacts with ZFHX3 in prostate cancer cells via multiple domains of ZFHX3, as revealed by IP and IB analyses (Fig. 4); the same promoter site of MYC can be bound by both ERβ and ZFHX3, and loss of ZFHX3 prevented ERβ from binding to the site (Fig. 5).