Rapamycin Antagonizes BCRP-Mediated Drug Resistance Through the PI3K/Akt/mTOR Signaling Pathway in mPRα-Positive Breast Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33912444", "kind": "science-record", "revision": 6, "content_hash": "sha256:9f51d7e427796dd77b2dacd15b2ae90c70f57446d776d92cafe5fbf12a936dd2", "created_at": "2026-11-01T15:41:33Z", "updated_at": "2026-11-01T21:25:14Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Rapamycin Antagonizes BCRP-Mediated Drug Resistance Through the PI3K/Akt/mTOR Signaling Pathway in mPRα-Positive Breast Cancer.", "doi": "10.3389/fonc.2021.608570", "pmid": "33912444", "authors": ["Jing Zhang", "Jing Hu", "Weiwei Li", "Chunyan Zhang", "Peng Su", "Yan Wang", "Wei Sun", "Xiao Wang", "Li Li", "Xiaojuan Wu"], "journal": "Frontiers in oncology", "year": 2021, "abstract": "PURPOSE: Overexpression of breast cancer (BCa) resistance protein (BCRP) is detected in approximately 30% of BCa cases. BCRP indicates a poor response to chemotherapy, and it has become a classic target to overcome drug-resistant tumor cells. In this study, we aimed to explore the mechanism of BCRP overexpression and a strategy to reverse this overexpression in invasive BCa.\nMETHODS: BCRP expression in BCa tissues was determined by immunohistochemistry. GSE25066 was downloaded from the NCBI GEO database. Western blot was used to determine the expression of key molecules in vitro. Cell counting kit-8 assays were used to assess the drug response of BCa cells.\nRESULTS: Our results suggested that BCRP is an independent risk factor for BCa. We further established that upon 17α-PG binding, membrane progesterone receptor α (mPRα) promoted BCRP expression via the PI3K/Akt/mTOR signaling pathway. mPRα physically interacted with p-Akt1 S473. Moreover, rapamycin, an inhibitor of mTOR complex 1 (mTORC1), downregulated BCRP expression and enhanced the effects of particular drugs, including doxorubicin and paclitaxel.\nCONCLUSION: BCRP is a potential biomarker of poor prognosis in BCa. BCRP expression is regulated by 17α-PG in mPRα-positive BCa cells through the PI3K/Akt/mTOR signaling pathway. Rapamycin might enhance the therapeutic effect of chemotherapy agents in mPRα-positive MDA-MB-453/BCRP cells and might be a therapeutic option for mPRα-positive invasive BCa with BCRP overexpression.", "claims": [{"id": "claim-method", "statement": "The correlations between BCRP expression and overall survival curves were plotted by the Kaplan–Meier method and compared with the log-rank test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33912444", "locator": "sections[8] \"Statistical Analysis\" paragraph 3", "quote": "The correlations between BCRP expression and overall survival curves were plotted by the Kaplan–Meier method and compared with the log-rank test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . 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