Hu Jing, Zhang Hui, Liu Long, Han Bo, Zhou Gengyin, Su Peng
Department of Pathology, Qilu Hospital of Shandong University, Jinan, China.
Front Oncol. 2020 Jun 30;10:934. doi: 10.3389/fonc.2020.00934. eCollection 2020.
Multidrug resistance (MDR) is the major obstruction in the successful treatment of breast cancer (BCa). The elucidation of molecular events that confer chemoresistance of BCa is of major therapeutic importance. Several studies have elucidated the correlation of TRPS1 and BCa. Here we focused on the role of TRPS1 in acquisition of chemoresistance, and reported a unique role of TRPS1 renders BCa cells resistant to chemotherapeutic drugs via the regulation of BCRP expression. Bioinformation analysis based on publicly available BCa data suggested that TRPS1 overexpression linked to chemoresistance. Mechanistically, TRPS1 regulated BCRP expression and efflux transportation. Overexpression of TRPS1 led to upregulation of BCRP while its inhibition resulted in repression of BCRP. The correlation of TRPS1 and BCRP was further confirmed by immunohistochemistry in 180 BCa samples. MTT assay demonstrated that manipulation of TRPS1 expression affects the chemosensitivity of BCa cells. In total, high expression of TRPS1 confers MDR of BCa which is mediated by BCRP. Our data demonstrated a new insight into mechanisms and strategies to overcome chemoresistance in BCa.
多药耐药性（MDR）是乳腺癌（BCa）成功治疗的主要障碍。阐明赋予BCa化疗耐药性的分子事件具有重要的治疗意义。多项研究阐明了TRPS1与BCa的相关性。在此，我们聚焦于TRPS1在获得化疗耐药性中的作用，并报道了TRPS1的独特作用，即通过调节BCRP表达使BCa细胞对化疗药物产生耐药性。基于公开可用的BCa数据进行的生物信息分析表明，TRPS1过表达与化疗耐药性相关。从机制上讲，TRPS1调节BCRP表达和外排转运。TRPS1的过表达导致BCRP上调，而其抑制则导致BCRP下调。通过对180例BCa样本进行免疫组织化学进一步证实了TRPS1与BCRP的相关性。MTT试验表明，TRPS1表达的改变会影响BCa细胞的化疗敏感性。总体而言，TRPS1的高表达赋予BCa多药耐药性，这是由BCRP介导的。我们的数据为克服BCa化疗耐药性的机制和策略提供了新的见解。
