Abstract B58: Inflammatory signaling regulates osteoprotegerin expression in breast cancer cells

Osteoprotegerin (OPG) is a secreted member of the Tumor Necrosis Factor family. In addition to the functional roles of OPG in bone metabolism and apoptosis, there is growing evidence of the tumor promoting role of OPG in breast cancer. We have previously shown OPG can promote the invasion and metastasis of triple negative breast cancer cells. To understand the regulation of OPG, we are investigating the molecular mechanisms that control OPG expression in breast cancer cells.Breast cancer cell lines MDA-MB-231 and MDA-MB-436 (triple negative); SKBR-3 and HCC1954 (Human Epidermal Growth Factor Receptor 2 positive; HER2+); ZR75-1 and MCF-7 (Estrogen Receptor positive; ER+) were treated with Interleukin1beta (IL1-beta) for 24 hours. Levels of OPG mRNA and secreted OPG protein were analyzed by real time RT-PCR and ELISA, respectively. IL1-beta induced OPG expression regardless of basal OPG levels, with the exception of MDA-MB-231 which exhibited relatively moderate OPG induction.To explore the signaling mechanisms downstream of IL1-beta, we treated breast cancer cells with MAP kinase inhibitors in the presence of IL1-beta and examined the effects on OPG protein induction. Both p38 MAPK inhibitors, SB203580 and SB202190, were observed to partially blocked OPG induction by IL1-beta. Western blot analysis confirmed IL1-beta induced p38 phosphorylation.Additionally, we examined the effects of NFkappaB p65 binding to potential NFKappaB binding sites within the OPG promoter upon IL1-bet...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Tumor Microenvironment and Immunotherapy: Poster Presentations - Proffered Abstracts Source Type: research