Abstract 724: FE65 in breast cancer patients and its clinicopathological significance

Abstract

Abstract FE65 is well known to bind with amyloid precursor protein (APP), translocate FE65-APP complex into nucleus and modulate gene transcription. APP was reported to be closely associated with breast cancer progression but clinical significance of FE65 has remained virtually unknow. We first studied 88 surgical pathology specimens with their clinicopathological factors. Results showed nuclear FE65 immunoreactivity was significant positively correlated with estrogen receptor (ER) status (P=0.054) and inversely with histological grade of the patients(P=0.038). We then analyzed 145 ER positive cases which include 44 ductal carcinomas in situ (DCIS) cases and 101 invasive ductal carcinoma (IDC) cases. The number of FE65 positive carcinoma cells was significantly higher in IDC than DCIS (P=0.0395). We then performed in vitro wound healing assay, which demonstrated that FE65 knock-down cells migrated slower than control groups (P=0.0495). FE65 formed the complex with APP and in order to further elucidate their detailed intracellular binding status, proximity ligation assay (PLA) was employed. Binding of APP and FE65 was detected in the cytoplasm with that of ER and FE65 in the nucleus. These results demonstrated that FE65 first bound to APP in the cytoplasm and was then released into the nucleus after phosphorylation of APP. This released FE65 in the nuclei could interact with ER to promote cell migration. Based on those results above, we then conducted the WST-8 assay to further elucidate the possible involvement of FE65 in cell survival. FE65 influenced response of tamoxifen in breast carcinoma cells, and the survival rate of those knocked down by FE65 siRNA was significantly higher than that of the control siRNA group(P=0.0039), indicating that FE65 could contribute to increase the sensitivity of tamoxifen action.In summary, FE65 was demonstrated to stimulate cell proliferation and migration, possibly as a result of the interaction of FE65 with APP in the cytoplasm and ER in the nuclei. In addition, FE65 could enhance the actions of tamoxifen by increasing ER expression and subsequent availability of its binding to ER. Citation Format: Junyao Xu, Erina Iwabuchi, Yasuhiro Miki, Ayako Kanai, Takanori Ishida, Hironobu Sasano. FE65 in breast cancer patients and its clinicopathological significance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 724.