Abstract
Abstract Background: We previously demonstrated a prognostic role of exosomal Del-1 with breast cancer patients. However, the mechanisms of Del-1 expression are barely understood. Development of resistance to tamoxifen is an important clinical issue in the treatment of breast cancer. Accordingly, we investigated the function of Del-1 in tamoxifen-resistant (TAMR) breast cancer cell line and tumor specimens. Materials and Methods: Del-1 expression in MCF7 and TAMR MCF7 cells was performed by quantitative RT-PCR, western blot, and ELISA. The effects of Del-1 with RNA interference on proliferation, migration and invasion of TAMR MCF7 cells were observed by MTT, wound healing and Matrigel transwell assay. Meanwhile, the tumoral expression of Del-1 was determined immunohistochemistry (IHC) from 10 tamoxifen resistant-breast cancer patients. Tumor tissue before (tamoxifen sensitive) and after tamoxifen resistance were assessed. Results: Del-1 was highly expressed in TAMR MCF7 cells compared to MCF7 cells (p<0.001). And the expression of secretory del-1 was also increased in the culture media of TAMR MCF7 cells. Moreover, down-regulation of Del-1 significantly inhibited the proliferation and migration of TAMR MCF7 cells. There was no difference in the invasion of TAMR MCF7 cells. Increased Del-1 expression was preferentially observed in in TAMR tumor tissues when compared to tamoxifen sensitive or normal breast tissue. Conclusion: Prominent expression of Del-1 in TAMR MCF7 cells was associated with the proliferation and migration of TAMR MCF7 cells. And the tumoral expression of Del-1 was also significantly associated with tamoxifen resistance. These results suggest that the expression of Del-1 promote tamoxifen resistance in breast cancer cells and could be a novel target for anti-breast cancer treatment. Citation Format: Yee Soo Chae, Jong Gwang Kim, Jae-Hwan Jeong, Soo Jung Lee, Jeeyeon Lee, Jin Hyang Jung, Ho Yong Park, Moon-Chang Baek, Senten Richard J, Ji Young Park. Del-1 promotes the proliferation and migration of tamoxifen-resistant breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4892.
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