Significant Association of Estrogen Receptor-beta Isoforms and Coactivators in Breast Cancer Subtypes

Nuclear receptor coregulators are the principal regulators of Estrogen Receptor (ER)-mediated transcription. ER beta, an ER subtype first identified in 1996, is associated with poor outcomes in breast cancer (BCa) subtypes, and the coexpression of the ER beta 1 isoform and AIB-1 and TIF-2 coactivators in BCa-associated myofibroblasts is associated with high-grade BCa. We aimed to identify the specific coactivators that are involved in the progression of ER beta-expressing BCa. ER beta isoforms, coactivators, and prognostic markers were tested using standard immunohistochemistry. AIB-1, TIF-2, NF-kB, p-c-Jun, and/or cyclin D1 were differentially correlated with ER beta isoform expression in the BCa subtypes and subgroups. The coexpression of the ER beta 5 and/or ER beta 1 isoforms and the coactivators were found to be correlated with a high expression of P53, Ki-67, and Her2/neu and large-sized and/or high-grade tumors in BCa. Our study supports the notion that ER beta isoforms and coactivators seemingly coregulate the proliferation and progression of BCa and may provide insight into the potential therapeutic uses of the coactivators in BCa.