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Updated: Jun 30, 2026
06:07
Screening for Phytoestrogens using a Cell-based Estrogen Receptor β Reporter Assay
Published on: June 7, 2020
Clusterin: a potential target for improving response to antiestrogens.
Sara Toffanin1, Maria Grazia Daidone, Patrizia Miodini
1Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, I-20133 Milano, Italy.
International Journal of Oncology
|September 25, 2008
Summary
Targeting cytoplasmic clusterin (CLU) may overcome antiestrogen resistance in breast cancer. Down-regulating CLU restored sensitivity to toremifene in resistant cells, suggesting CLU as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Antiestrogens are primary treatments for estrogen receptor-positive (ER+) breast cancer.
- Therapeutic resistance develops in up to 40% of patients, leading to metastatic disease.
- Molecular mechanisms underlying antiestrogen resistance are not fully understood.
Purpose of the Study:
- To investigate the role of cytoplasmic clusterin (CLU) in antiestrogen resistance in ER+ breast cancer.
- To determine if targeting CLU can restore sensitivity to antiestrogens.
Main Methods:
- Utilized ER+ antiestrogen-sensitive (MCF-7, 734B) and resistant (T47D) cell lines.
- Employed siRNA to down-regulate cytoplasmic clusterin expression.
- Assessed the effect of CLU down-regulation on cell growth and response to toremifene and tamoxifen.
Main Results:
- Resistant cells exhibited higher basal cytoplasmic clusterin levels than sensitive cells.
- Antiestrogen treatments upregulated clusterin in both sensitive and resistant cell lines.
- siRNA-mediated CLU down-regulation significantly decreased cell growth exclusively in the resistant cell line, restoring sensitivity to toremifene.
Conclusions:
- Basal clusterin levels are elevated in antiestrogen-resistant cells.
- Clusterin is upregulated by antiestrogens irrespective of cell line sensitivity.
- Targeting cytoplasmic clusterin represents a potential therapeutic strategy to overcome antiestrogen resistance in breast cancer.
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