ESR2 and cancer: For example, ERβ exhibits antitumor activity, unlike ERα.9 Several studies have shown that overexpression of ERβ reduces cell proliferation, whereas knockdown of ERβ enhances cell proliferation in cancer cells.10,11 As transcription factors, ERα and ERβ share many target genes; however, ERβ activates a unique set of genes12,13 via its direct DNA binding or its interactions with other transcription factors.12,14 GBM cells uniquely express ERβ,15 further, recent evidence indicates that the expression of ERβ is significantly reduced during GBM progression.