The Affiliated Hospital of Jiaxing University, Jiaxing, China.
J Int Med Res. 2022 Mar;50(3):3000605221082895. doi: 10.1177/03000605221082895.
Gonadotropin-releasing hormone receptor (GnRHR) is expressed in several malignant tumors and inhibits the proliferation and metastasis of cancer cells, but its role in triple-negative breast cancers (TNBCs) is unclear. This study investigated the biological effects of GnRHR and their influence on TNBC prognosis.
The GSE21653 database was used to obtain information about GnRHR expression and clinicopathological factors in patients with TNBC. GnRHR was activated in cultured MDA-MB-231 and MDA-MB-468 cells by leuprolide acetate and antagonized by elagolix sodium. Cell proliferation was assessed by the cell counting kit-8 and colony formation assays. Cell metastasis was detected by the wound healing assay and Transwell assay. Apoptosis and the cell cycle were investigated by flow cytometry. GnRHR protein expression was determined by western blotting.
GnRHR mRNA expression was significantly higher in patients with TNBC than in hormone receptor+/human epidermal growth factor receptor (HER)2- and HER2+ patients with breast cancer. Patients with high GnRHR expression had significantly better disease-free survival than those with lower expression. Activated GnRHR significantly inhibited cell proliferation and metastasis, increased apoptosis, and enhanced GnRHR protein expression levels.
GnRHR inhibits TNBC proliferation and metastasis, suggesting it could be targeted for TNBC treatment.
促性腺激素释放激素受体(GnRHR)在多种恶性肿瘤中表达,并抑制癌细胞的增殖和转移,但在三阴性乳腺癌(TNBC)中的作用尚不清楚。本研究探讨了 GnRHR 的生物学效应及其对 TNBC 预后的影响。
使用 GSE21653 数据库获取 TNBC 患者中 GnRHR 表达和临床病理因素的信息。用醋酸亮丙瑞林激活培养的 MDA-MB-231 和 MDA-MB-468 细胞,用 Elagolix 钠拮抗 GnRHR。通过细胞计数试剂盒-8 和集落形成实验评估细胞增殖。通过划痕愈合实验和 Transwell 实验检测细胞迁移。通过流式细胞术研究细胞凋亡和细胞周期。通过 Western blot 测定 GnRHR 蛋白表达。
与激素受体+/人表皮生长因子受体(HER)2-和 HER2+乳腺癌患者相比,TNBC 患者的 GnRHR mRNA 表达显著升高。高 GnRHR 表达的患者无病生存率显著高于低表达的患者。激活的 GnRHR 显著抑制细胞增殖和转移,增加细胞凋亡,并增强 GnRHR 蛋白表达水平。
GnRHR 抑制 TNBC 的增殖和转移,提示其可能成为 TNBC 治疗的靶点。