ArticleBreast cancer research and treatment2021
Reduced menin expression leads to decreased ERα expression and is correlated with the occurrence of human luminal B-like and ER-negative breast cancer subtypes.
Article in Breast cancer research and treatment, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Hsa-miR-149-5p targets Men1 to inhibit the progression of gastric cancer through the HSPA6/JNK pathway.Cancer cell international · 2026Article
- Associations of selected atypical non-neuroendocrine cancers with multiple endocrine neoplasia type 1.Journal of the Endocrine Society · 2026Article
- Harnessing the Role ofInternational journal of molecular sciences · 2025Article
- Menin in Cancer.Genes · 2024Review
- The risk of concurrent malignancies in patients with multiple endocrine neoplasia type 1: insights into clinical characteristics of those with multiple endocrine neoplasia type 1.Journal of endocrinological investigation · 2024Article
- Selective Concurrence of the Long Non-Coding RNA MALAT1 and the Polycomb Repressive Complex 2 to Promoter Regions of Active Genes in MCF7 Breast Cancer Cells.Current issues in molecular biology · 2023Article
- Combinatorial targeting of a chromatin complex comprising Dot1L, menin and the tyrosine kinase BAZ1B reveals a new therapeutic vulnerability of endocrine therapy-resistant breast cancer.Breast cancer research : BCR · 2022Article
- Genetic Deletion of Menin in Mouse Mesenchymal Stem Cells: An Experimental and Computational Analysis.JBMR plus · 2022Article
- Beyond the "3 Ps": A critical appraisal of the non-endocrine manifestations of multiple endocrine neoplasia type 1.Frontiers in endocrinology · 2022Review
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeMenin, encoded by the MEN1 gene, was recently reported to be involved in breast cancers, though the underlying mechanisms remain elusive. In the current study, we sought to further determine its role in mammary cells.
methodsMenin expression in mammary lesions from mammary-specific Men1 mutant mice was detected using immunofluorescence staining. RT-qPCR and western blot were performed to determine the role of menin in ERα expression in human breast cancer cell lines. ChIP-qPCR and reporter gene assays were carried out to dissect the action of menin on the proximal ESR1 promoter. Menin expression in female patients with breast cancer was analyzed and its correlation with breast cancer subtypes was investigated.
resultsImmunofluorescence staining revealed that early mammary neoplasia in Men1 mutant mice displayed weak ERα expression. Furthermore, MEN1 silencing led to both reduced ESR1 mRNA and ERα protein expression in MCF7 and T47D cells. To further dissect the regulation of ESR1 transcription by menin, we examined whether and in which way menin could regulate the proximal ESR1 promoter, which has not been fully explored. Using ChIP analysis and reporter gene assays covering - 2500 bp to + 2000 bp of the TSS position, we showed that the activity of the proximal ESR1 promoter was markedly reduced upon menin downregulation independently of H3K4me3 status. Importantly, by analyzing the expression of menin in 354 human breast cancers, we found that a lower expression was associated with ER-negative breast cancer (P = 0.041). Moreover, among the 294 ER-positive breast cancer samples, reduced menin expression was not only associated with larger tumors (P = 0.01) and higher SBR grades (P = 0.005) but also with the luminal B-like breast cancer subtype (P = 0.006). Consistent with our clinical data, we demonstrated that GATA3 and FOXA1, co-factors in ESR1 regulation, interact physically with menin in MCF7 cells, and MEN1 knockdown led to altered protein expression of GATA3, the latter being a known marker of the luminal A subtype, in MCF7 cells.
conclusionTaken together, our data provide clues to the important role of menin in ERα regulation and the formation of breast cancer subtypes.
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