Evidence for transcriptional activation of ER alpha by IL-1B in breast cancer cells

Estrogen is mitogenic in breast cancer where IL-1 beta also fulfils a role. The aim of this study was to determine any relationship between IL-1 beta and ER alpha in breast cancer. By RT-PCR, 26/77 tumours expressed IL-1 beta , and 57/77 expressed ER alpha. Samples which were IL-1 beta positive were categorised against those which expressed ERa. Of the 26 tumours which expr essed IL-1 beta, all were ER alpha positive. We next examined whether IL-1 beta could directly activate ERa. MCF-7 cells stably transfected with a pla smid reporter (ERE-TK-LUC) were incubated with either 17 beta-estradiol (E- 2, 10(-9)-10(-13) M), IL-1 beta (10 ng/ml), the pure antiestrogen ZM 182780 (10 nM) or combinations of these substances. Transcriptional activity was measured in cell lysates 48 h later. E-2 caused a dose-dependent increase i n luciferase activity. With IL-1 beta, transcriptional activity was typical ly half of the E-2 response. To determine the role of the IL-1 receptor, pa rallel cultures were incubated with IL-l receptor antagonist. This reduced, but did not completely block the effect of IL-1 beta, suggesting that IL-1 beta was affecting transcriptional activity via another pathway. Confirmat ion that the effect was via ER alpha was verified using the pure antiestrog en, ZM 182370, which completely abrogated the effects of E-2, when added al one or in combination with IL-1 beta. These results provide compelling evid ence for direct transcriptional activation of ER alpha by IL-1 beta. Intera ctions of these factors may thus modulate hormonal activity in human breast tumours.