Abstract 4451: Novel orphan G-protein-coupled receptor is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma

Abstract

Abstract Alterations in cellular pathways related to both endocrine and angiogenic factors may contribute to breast cancer progression. Inhibition of the elevated levels of these pathways is associated with clinical benefits. However, underlying mechanisms by which endocrine-related pathways and angiogenic factor signaling cooperatively promote breast cancer progression remain unclear. In this study, we report that novel orphan G-protein-coupled receptor (GPCR), GPR YJ, is oncogenic and mediates anti-estrogen resistance in breast cancer. GPR YJ is overexpressed in breast cancer cells and tissues, where elevated expression correlates with high tumor grade. Also, GPR YJ induces the expression of several angiogenic factors (VEGF, bFGF and IL-8), as well as ErbB (amphiregulin, epiregulin and neuregulins), which activate their respective pathways, leading to increased cell proliferation and survival, enhanced anchorage-independent growth, and promoted migration and invasion. In vivo, GPR YJ promotes the formation of large, well-vascularized tumors that metastasize to distant organs such as lymph nodes, lung and liver. Thus, deregulated expression of GPR YJ contributes to breast cancer progression and metastasis by inducing several growth factors that alter tumor-specific cell fates and the tumor stromal microenvironment. Citation Format: Yu Jin Lee, Kyeong Jin Shin, Soo-Ah Park, Sung Ho Ryu, Pann-Ghill Suh. Novel orphan G-protein-coupled receptor is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4451. doi:10.1158/1538-7445.AM2014-4451