Abstract 48: Identification of a novel binding protein playing a critical role in HER2 activation in lung cancer cells

Abstract

Abstract Human epidermal growth factor receptor 2 (HER2) is a member of epidermal growth factor receptor (EGFR) family. Previous studies have revealed that many kinds of malignant tumors have genetic mutations or amplification of HER2, indicating that HER2 alterations are oncogenic. Many kinds of HER2 targeted therapies are effective to HER2 positive tumors, but those treated tumors often get resistance to drugs. Thus, to elucidate HER2 related pathway in cancer biology is important to develop new therapeutic strategy for cancers. Recently, we newly identified a protein X (a temporary name) as a novel binding protein to HER2 with immunoprecipitation and following LC-Ms/Ms analysis. The protein generally expressed in lung and breast cancers at remarkable level. We constructed plasmid vectors carrying wild type HER2 and gene X. These vectors were simultaneously introduced to HEK293T cells to examine the binding ability of protein X and HER2 as well as the effect of gene X on HER2-mediated signal-transduction pathway. The approach clearly showed that the expression of gene X, resulted in phosphorylation of HER2 and subsequent activation of oncogenic effector molecules. We next constructed several kinds of gene X-truncated variants and subjected to the binding assay to look for the binding domain of gene X to HER2. The analysis showed that N-terminal head domain of gene X was essential for the HER2 binding. This domain has an ability to induce HER2 phosphorylation and subsequent activation of the effector kinase, ERK. In conclusion, we found that gene X is a novel binding protein to HER2 and has a role in HER2 activation. Citation Format: Tomoaki Ohtsuka, Masakiyo Sakaguchi, Katsuyoshi Takata, Shinsuke Hashida, Mototsugu Watanabe, Ken Suzawa, Yuho Maki, Hiromasa Yamamoto, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Shinichiro Miyoshi, Shinichi Toyooka. Identification of a novel binding protein playing a critical role in HER2 activation in lung cancer cells. [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 48. doi:10.1158/1538-7445.AM2015-48