ArticleBreast cancer research and treatment2020
Histone methyltransferases regulate the transcriptional expression of ERα and the proliferation of tamoxifen-resistant breast cancer cells.
Article in Breast cancer research and treatment, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Epigenetic plasticity in cancer drug resistance: mechanistic insights and strategies for therapeutic intervention.Acta pharmacologica Sinica · 2026Review
- Lipid metabolism reprogramming: key mechanism of breast cancer endocrine therapy resistance.Frontiers in oncology · 2026Review
- Contrasting roles of KMT2C and KMT2D in breast cancer.Scientific reports · 2025Article
- The role of HOXA1 in cancer and targeted therapy.Medical oncology (Northwood, London, England) · 2025Review
- Secreted LGALS3BP facilitates distant metastasis of breast cancer.Breast cancer research : BCR · 2025Article
- Atypical Hippo signaling network: uncovering novel insights into head and neck cancer biology and advancements in precision intervention.Frontiers in cell and developmental biology · 2025Review
- Crosstalk of methylation and tamoxifen in breast cancer (Review).Molecular medicine reports · 2024Review
- WDR82-Mediated H3K4me3 Is Associated with Tumor Proliferation and Therapeutic Efficacy in Pediatric High-Grade Gliomas.Cancers · 2023Article
- The Role of Histone Modification in DNA Replication-Coupled Nucleosome Assembly and Cancer.International journal of molecular sciences · 2023Review
- Review
- Stilbenes: a promising small molecule modulator for epigenetic regulation in human diseases.Frontiers in pharmacology · 2023Review
- Epigenetic Factors as Etiological Agents, Diagnostic Markers, and Therapeutic Targets for Luminal Breast Cancer.Biomedicines · 2022Review
- Article
- Histone modification and histone modification-targeted anti-cancer drugs in breast cancer: Fundamentals and beyond.Frontiers in pharmacology · 2022Review
- HNRNPA2B1 regulates tamoxifen- and fulvestrant-sensitivity and hallmarks of endocrine resistance in breast cancer cells.Cancer letters · 2021Article
- KMT2C is a potential biomarker of prognosis and chemotherapy sensitivity in breast cancer.Breast cancer research and treatment · 2021Article
- The MLL3/4 H3K4 methyltransferase complex in establishing an active enhancer landscape.Biochemical Society transactions · 2021Review
- Review
- Targeting Histone Modifications in Breast Cancer: A Precise Weapon on the Way.Frontiers in cell and developmental biology · 2021Review
- Aberrant Activity of Histone-Lysine N-Methyltransferase 2 (KMT2) Complexes in Oncogenesis.International journal of molecular sciences · 2020Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
purposeAlthough tamoxifen remains the frontline treatment for ERα-positive breast cancers, resistance to this drug limits its clinical efficacy. Most tamoxifen-resistant patients retain ERα expression which may support growth and progression of breast cancers. Therefore, we investigated epigenetic regulation of ERα that may provide a rationale for targeting ERα in these patients.
methodsExpression levels of the mixed-lineage leukemia (MLL) family of proteins in tamoxifen-resistant breast cancer cells and publicly available breast cancer patient data sets were analyzed. Histone methylation levels in ERα promoter regions were assessed using chromatin immunoprecipitation. Expression levels of ERα and its target gene were analyzed using western blotting and real-time qPCR. Cell-cycle was analyzed by flow cytometry.
resultsThe expression of MLL3 and SET-domain-containing 1A (SET1A) were increased in tamoxifen-resistant breast cancers. An MLL3 chromatin immunoprecipitation-sequencing data analysis and chromatin immunoprecipitation experiments for MLL3 and SET1A suggested that these proteins bound to enhancer or intron regions of the ESR1 gene and regulated histone H3K4 methylation status. Depletion of MLL3 or SET1A downregulated the expression level of ERα and inhibited the growth of tamoxifen-resistant breast cancer cells. Additional treatment with fulvestrant resulted in a synergistic reduction of ERα levels and the growth of the cells.
conclusionsThe enhanced expression of MLL3 and SET1A in tamoxifen-resistant breast cancer cells supported the ERα-dependent growth of these cells by increasing ERα expression. Our results suggest that targeting these histone methyltransferases might provide an attractive strategy to overcome endocrine resistance.
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