ArticleBreast cancer research : BCR2011
Targeting cholesterol-rich microdomains to circumvent tamoxifen-resistant breast cancer.
Article in Breast cancer research : BCR, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 31 citations in OpenAlex.
- Cyclodextrins as Modulators of Regulated Cell Death: Implications for Immunometabolism and Therapeutic Innovation.Pharmaceutics · 2026Review
- ZMIZ1 lactylation induces tamoxifen resistance in breast cancer through increasing transcriptional activity of Nanog to impact cell stemness and cholesterol uptake.Cell biology and toxicology · 2025Article
- Research progress on cholesterol metabolism and tumor therapy.Discover oncology · 2025Review
- Lipid metabolic reprograming: the unsung hero in breast cancer progression and tumor microenvironment.Molecular cancer · 2025Review
- Unnatural Peptide Assemblies Rapidly Deplete Cholesterol and Potently Inhibit Cancer Cells.Journal of the American Chemical Society · 2024Article
- An Update on Tamoxifen and the Chemo-Preventive Potential of Vitamin E in Breast Cancer Management.Journal of personalized medicine · 2023Review
- microRNAs targeting cellular cholesterol: implications for combating anticancer drug resistance.Genes & cancer · 2020Article
- Article
- Dehydroepiandrosterone Activation of G-protein-coupled Estrogen Receptor Rapidly Stimulates MicroRNA-21 Transcription in Human Hepatocellular Carcinoma Cells.The Journal of biological chemistry · 2015Article
- Mononuclear Phagocyte-Derived Microparticulate Caspase-1 Induces Pulmonary Vascular Endothelial Cell Injury.PloS one · 2015Article
- Targeting Intracellular Cholesterol is a Novel Therapeutic Strategy for Cancer Treatment.Journal of cancer science & therapy · 2014Article
- Role of endoplasmic reticulum stress induction by the plant toxin, persin, in overcoming resistance to the apoptotic effects of tamoxifen in human breast cancer cells.British journal of cancer · 2013Article
- Personalized medicine and pharmacogenetic biomarkers: progress in molecular oncology testing.Expert review of molecular diagnostics · 2012Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
introductionAdjuvant treatment with tamoxifen substantially improves survival of women with estrogen-receptor positive (ER+) tumors. Tamoxifen resistance (TAMR) limits clinical benefit. RRR-α-tocopherol ether-linked acetic acid analogue (α-TEA) is a small bioactive lipid with potent anticancer activity. We evaluated the ability of α-TEA in the presence of tamoxifen to circumvent TAMR in human breast cancer cell lines.
methodsTwo genotypically matched sets of TAM-sensitive (TAMS) and TAM-resistant (TAMR) human breast cancer cell lines were assessed for signal-transduction events with Western blotting, apoptosis induction with Annexin V-FITC/PI assays, and characterization of cholesterol-rich microdomains with fluorescence staining. Critical involvement of selected mediators was determined by using RNA interference and chemical inhibitors.
resultsGrowth-factor receptors (total and phosphorylated forms of HER-1 and HER-2), their downstream prosurvival mediators pAkt, pmTOR, and pERK1/2, phosphorylated form of estrogen receptor-α (pER-α at Ser-167 and Ser-118, and cholesterol-rich lipid microdomains were highly amplified in TAMR cell lines and enhanced by treatment with TAM. α-TEA disrupted cholesterol-rich microdomains, acted cooperatively with TAM to reduce prosurvival mediators, and induced DR5-mediated mitochondria-dependent apoptosis via an endoplasmic reticulum stress-triggered pro-death pJNK/CHOP/DR5 amplification loop. Furthermore, methyl-β-cyclodextrin (MβCD), a chemical disruptor of cholesterol rich microdomains, acted cooperatively with TAM to reduce prosurvival mediators and to induce apoptosis.
conclusionsData for the first time document that targeting cholesterol-rich lipid microdomains is a potential strategy to circumvent TAMR, and the combination of α-TEA + TAM can circumvent TAMR by suppression of prosurvival signaling via disruption of cholesterol-rich lipid microdomains and activation of apoptotic pathways via induction of endoplasmic reticulum stress.
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