Interestingly, expression of ERβ1 decreases with GBM progression with concomitant increase in the expression of ERβ5.19 Since, ERβ1 functions as tumor suppressor and ERβ5 functions as an oncogene, the observed alteration in the expression of ERβ isoform may reflect adaptation of selection pressures. This evidence concerns the gene ESR2 and glioblastoma.