Department of Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Oncology. 2019;97(3):180-188. doi: 10.1159/000501340. Epub 2019 Jul 22.
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.
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.
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.
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.
激素受体阳性乳腺癌占乳腺癌病例的近三分之二；它最终在内分泌治疗过程中产生耐药性，并变得更具侵袭性。本研究评估了发育内皮定位（Del）-1 在他莫昔芬耐药（TAM-R）乳腺癌中的作用。
评估了复发性 TAM-R 乳腺癌组织中 Del-1 的表达，并与同一患者原始肿瘤组织中的表达进行了比较。通过定量实时 PCR、western blot 和酶联免疫吸附试验评估了 Del-1 在 TAM-R 细胞中的表达。通过划痕愈合和 Matrigel 侵袭试验评估了 Del-1 敲低对 TAM-R 细胞增殖、迁移和侵袭的影响。
与内分泌治疗前的原始肿瘤组织相比，复发性乳腺癌中 Del-1 的表达更高。TAM-R 中 Del-1 mRNA 上调，并且 Del-1 的小干扰 RNA 介导的敲低抑制了 TAM-R 细胞的迁移和增殖，同时部分恢复了 TAM 敏感性。通过敲低 Del-1 恢复了 TAM 耐药性。
TAM-R 乳腺癌的特征是 Del-1 过表达，通过 Del-1 耗竭可以抑制肿瘤进展，从而恢复 TAM 敏感性。因此，靶向 Del-1 的治疗策略可能对治疗激素耐药性乳腺癌有效。
