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TRPS1 Confers Multidrug Resistance of Breast Cancer Cells by Regulating BCRP Expression
Jing Hu1, Hui Zhang1, Long Liu1
1Department of Pathology, Qilu Hospital of Shandong University, Jinan, China.
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.
Insights
High TRPS1 expression in breast cancer (BCa) drives multidrug resistance (MDR) by increasing BCRP, a key transporter. Inhibiting TRPS1 may restore chemosensitivity in BCa treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Multidrug resistance (MDR) significantly hinders effective breast cancer (BCa) treatment.
- Understanding the molecular mechanisms of chemoresistance is crucial for therapeutic advancement.
- Previous studies suggest a link between TRPS1 and breast cancer progression.
Purpose of the Study:
- To investigate the specific role of TRPS1 in the development of chemoresistance in breast cancer.
- To elucidate the molecular pathway through which TRPS1 influences drug resistance.
- To identify TRPS1 as a potential therapeutic target for overcoming MDR in BCa.
Main Methods:
- Bioinformatic analysis of publicly available breast cancer datasets.
- In vitro experiments involving manipulation of TRPS1 expression in BCa cells.
- Assessment of BCRP expression and function.
- Immunohistochemical analysis of TRPS1 and BCRP correlation in patient samples.
- MTT assays to evaluate chemosensitivity.
Main Results:
- TRPS1 overexpression was correlated with chemoresistance in breast cancer data.
- TRPS1 directly regulates the expression of BCRP, a drug efflux transporter.
- Upregulation of TRPS1 increased BCRP levels, while TRPS1 inhibition decreased BCRP.
- A significant correlation between TRPS1 and BCRP was observed in 180 BCa patient samples.
- Modulating TRPS1 expression altered the chemosensitivity of breast cancer cells.
Conclusions:
- High TRPS1 expression confers multidrug resistance in breast cancer.
- This MDR is mediated through the regulation of BCRP expression and function.
- TRPS1 represents a novel mechanism contributing to BCa chemoresistance.
- Targeting TRPS1 could offer a new strategy to overcome chemoresistance in breast cancer treatment.
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