Abstract 3826: The zinc transporters, ZnT5 and ZnT6, in breast cancer

Abstract

Abstract The zinc levels in breast cancer tissue were reported to be higher than those in normal tissue. In addition, the expression levels of zinc transporters, including ZnT5 and ZnT6, in breast cancer were reported to be higher than those in normal breast tissue. ZnT5 and ZnT6 have been also reported to contribute to the formation of heterodimers and be involved in several different biological functions. Among those, autotaxin, matrix metalloproteinase 9, and carbonic anhydrase IX, which have crucial roles in tumor formation, invasion, and metastasis, were reported to require ZnT5–ZnT6 heterodimers for their activation and secretion in the chicken DT40 cells. However, the functions of ZnT5 and ZnT6 heterodimers has remained virtually unknown in breast cancer. Therefore, we first immunolocalized ZnT5 and ZnT6 in pathology specimens of breast cancer. We examined 88 breast cancer specimens in this study. We then analyzed the interaction between ZnT5 and ZnT6 using proximity ligation assay (PLA) in breast cancer tissues and further evaluated cell proliferation and migration in ZnT5 knockdown MCF-7 and T-47D cells using siRNA. Immunohistochemical analysis revealed that the number of ZnT5-positive breast cancer cells was significantly higher in HER2-positive patients and the number of ZnT6-positive breast cancer cells was significantly higher in patients with low histological grade and high ER and PgR expressions. The number of ZnT5 and ZnT6 double-positive breast cancer cells tended to be associated with low stage (p = 0.0577). In addition, ZnT5 and ZnT6 interaction was detected using PLA through high expression of both ZnT5 and ZnT6 in breast cancer tissues. ZnT5 knockdown exerted no effect on cell proliferation in the presence of 100 µM ZnCl2 in MCF-7 and T-47D cells. The 100 µM ZnCl2 treatment inhibited cell migration in MCF-7 and T-47D cells but ZnT5 knockdown promoted cell migration. To the best of our knowledge, this is the first study demonstrating the expressions of ZnT5 and ZnT6 in breast cancer. The results of this study also indicated that both ZnT5 and ZnT6 could be involved in less aggressive subtypes of breast cancer possibly through inhibition of cell migration. Further studies are required to clarify the clinical significance of their interactions in patients with breast cancer. Citation Format: Erina Iwabuchi, Yasuhiro Miki, Takanori Ishida, Hironobu Sasano. The zinc transporters, ZnT5 and ZnT6, in breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3826.