Abstract 1198: Connexin 43 is an estrogen receptor β1 regulated gene in breast cancer

Abstract

Abstract Connexins are a family of transmembrane proteins that allow direct cell to cell communication. Normal human mammary epithelium expresses both connexin 43 (Cx43) and connexin 26 (Cx26) and when overexpressed, these connexins have been shown to act as tumor suppressors in human breast cancer. We have previously characterized two human breast cancer cells lines that inducibly overexpress estrogen receptor β1 (ERβ1) and we utilize these cells to examine the regulation of Cx43 by ERβ1 in human breast cancer. We observe that in both MCF7 and MDA-MB-231 cells that inducibly overexpress ERβ1, upon estradiol (E2) stimulation, there is a 4-fold or greater increase in Cx43 protein, regardless of whether cells are grown in two-dimensional (2D) or organotypic three-dimensional (3D) cell culture. Cx43 mRNA increases 2-fold upon ERβ1 induction and E2 stimulation of MDA-MB-231 cells with no co-incident change in Cx26 mRNA. Cx43 protein significantly increases upon treatment of cells with selective ERβ agonists, like DPN or genistein, but not with the ERα agonist PPT. Treatment of cells with ICI 182780 inhibits the E2 stimulated increase in Cx43 protein, while, the E2 stimulated increase was still seen in the presence of the anti-progestin RU486. Moreover, we observe a morphological shift in the appearance of MDA-MB-231 cells that overexpress ERβ1 when grown in 3D culture to that of a more differentiated-like organoid. Further work will involve an analysis of the interaction between ERβ1 and the Cx43 promoter. Taken together, the data suggests that Cx43 is an ERβ1 regulated gene. This research is funded by grants from CBCRA (Canadian Breast Cancer Research Alliance), CIHR (Canadian Institutes for Health Research), and CCMF (CancerCare Manitoba Foundation). EM is the recipient of a post-doctoral research fellowship from the Canadian Cancer Society Research Institute – Terry Fox Foundation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1198. doi:10.1158/1538-7445.AM2011-1198