Overcoming Tamoxifen Resistance by Regulation of Del-1 in Breast Cancer.
By: Jeeyeon Lee, Jae-Hwan Jeong, Jin Hyang Jung, Wan Wook Kim, Soo Jung Lee, Ji-Young Park, Jee Young Park, Seung Hee Kang, Eun Ae Kim, Jae Hyung Park, Yee Soo Chae, Ho Yong Park

Department of Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
2019-04-17; doi: 10.1159/000501340
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.



© 2019 S. Karger AG, Basel.

PMID:31330520






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