Abstract
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.
Highlights
To date, breast cancer (BCa) ranks first among female malignant tumor, accounting for 30%, and the second leading cause of cancer mortality in women, accounting for 15% [1]
Breast cancer resistance protein (BCRP) expression was scored for intensity (0 = negative; 1 = weak; 2 = moderate; 3 = strong) and the percentage of positive cells (0 = 0–10%; 1 = 10–40%; 2 = 40–70%; 3 = 70–100%)
One of the mechanisms of Multidrug resistance (MDR) is the elevated expression of ATPbinding cassette (ABC) transporters
Summary
Breast cancer (BCa) ranks first among female malignant tumor, accounting for 30%, and the second leading cause of cancer mortality in women, accounting for 15% [1]. Surgery is the predominant treatment of BCa. Chemotherapy may be used as adjuvant therapy to shrink the tumor before surgery or to prevent remission/relapse after surgery [2]. Multidrug resistance (MDR) is a major limitation for chemotherapy leading to treatment failure and tumor relapse [3, 4]. Breast cancer resistance protein (BCRP) belongs to the subfamily of G of the ABC transporter superfamily and has been extensively studied. Several studies have focused on potent inhibitor of BCRP to block the drug efflux activity [12]
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