Overcoming Tamoxifen Resistance by Regulation of Del-1 in Breast Cancer.

ABSTRACT

BACKGROUND: Hormone receptor-positive breast cancer accounts for nearly two-thirds of breast cancer cases; it ultimately acquires resistance during endocrine treatment and becomes more aggressive. This study evaluated the role of developmental endothelial locus (Del)-1 in tamoxifen-resistant (TAM-R) breast cancer. METHODS: Del-1 expression in recurrent TAM-R breast cancer tissue was evaluated and compared to that in the original tumor tissue from the same patients. Del-1 expression was also evaluated in TAM-R cells by quantitative real-time PCR, western blotting, and enzyme-linked immunosorbent assay. The effects of Del-1 knockdown on the proliferation, migration, and invasion of TAM-R cells was assessed with wound-healing and Matrigel transwell assays. RESULTS: Del-1 was more highly expressed in recurrent breast cancer as compared to the original tumor tissues before initiation of endocrine treatment. Del-1 mRNA was upregulated in TAM-R and small interfering RNA-mediated knockdown of Del-1 suppressed the migration and proliferation of TAM-R cells while partly restoring TAM sensitivity. And the TAM resistance was recovered by knockdown of Del-1. CONCLUSIONS: TAM-R breast cancer is characterized by Del-1 overexpression and tumor progression can be inhibited by Del-1 depletion, which restores TAM sensitivity. Thus, therapeutic strategies that target Del-1 may be effective for the treatment of hormone-resistant breast cancer.