Abstract 3367: BMP-6 regulates expression of androgen receptor via NF-κB signaling pathway and activated macrophages

Abstract

Prostate cancer (CaP) is the most common non-cutaneous cancer among men in the United States (US). Recent report estimated that around 233,000 new CaP cases will be occurred in 2014 and about 29,480 men will be death because of CaP in the US. Despite recent progress in CaP treatment, metastatic CaP patients still have a poor prognosis due to the inevitable emergence of castration resistant prostate cancer (CRPC). It has been reported that androgen hypersensitivity and tumor microenvironment were critical factors for developing CRPC. In the present study, we investigate the role of BMP-6 on androgen hypersensitivity in the context of macrophages. Initially, we co-cultured androgen responsive murine CaP cell lines TRAMP-C1 and PTEN-CaP8 with RAW 264.7 murine macrophage cell lines and treated with BMP-6. We found that androgen receptor (AR) expression was increased in both cell lines by treatment of BMP-6 and BAY 11-7082 NF-κB inhibitor neutralized this augmentation. The result indicates that NF-κB signaling pathway is involved in up-regulation of AR in CaP cells. To find which NF-κB is activated, we analyzed NF-κB signaling pathway with immunoblot and found that canonical NF-κB pathway was activated in CaP cells. Cytokines such as IL-6 and TNF-α are potential inducer of NF-κB signaling pathway and these cytokines were up-regulated in RAW cells in our co-culture system. Based on these observations, we suggest that BMP-6 potentially regulates expression of AR in CaP cells via activated macrophages and canonical NF-κB pathway.

Citation Format: Emma Wilcox, Seok Joo Kwon, Geun Taek Lee, Isaac Yi Kim. BMP-6 regulates expression of androgen receptor via NF-κB signaling pathway and activated macrophages. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3367. doi:10.1158/1538-7445.AM2015-3367