ArticleOncotarget2016
Estrogen receptor alpha (ERα/ESR1) mediates the p53-independent overexpression of MDM4/MDMX and MDM2 in human breast cancer.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Integrated in silico and in vitro evaluation of Camellia sinensis phytosomes in estrogen receptor-positive breast cancer.Scientific reports · 2026Article
- Biological and computer-aided evaluation of 3-methoxy-13α-estrone-16α-diphenylphosphine oxide as a new antiestrogenic agent.Scientific reports · 2025Article
- Cytotoxic and proapoptotic effects of alizarin in mice with Ehrlich solid tumor: novel insights into ERα-mediated MDM2/p-Rb/E2F1 signaling pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Differences in the role of Gper1 in colorectal cancer progression depending on sex.Oncology letters · 2025Article
- Interaction between Estrogen Receptors and p53: A Broader Role for Tamoxifen?Endocrinology · 2025Review
- Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor.Cell communication and signaling : CCS · 2024Article
- MDMX in Cancer: A Partner of p53 and a p53-Independent Effector.Biologics : targets & therapy · 2024Review
- MDM2- an indispensable player in tumorigenesis.Molecular biology reports · 2023Review
- Mechanism ofNutrients · 2022Article
- Modulation of BRCA1 mediated DNA damage repair by deregulated ER-α signaling in breast cancers.American journal of cancer research · 2022Article
- Novel genomic alteration in superficial esophageal squamous cell neoplasms in non-smoker non-drinker females.Scientific reports · 2021Article
- Estrogen Receptor-Alpha and p53 Status as Regulators of AMPK and mTOR in Luminal Breast Cancer.Cancers · 2021Article
- Mechanisms of TP53 Pathway Inactivation in Embryonic and Somatic Cells-Relevance for Understanding (Germ Cell) Tumorigenesis.International journal of molecular sciences · 2021Review
- Associations ofJournal of clinical medicine · 2021Article
- Role of Sex in the Therapeutic Targeting of p53 Circuitry.Frontiers in oncology · 2021Review
- MDM2 as a Rational Target for Intervention in CDK4/6 Inhibitor Resistant, Hormone Receptor Positive Breast Cancer.Frontiers in oncology · 2021Review
- The 40bp Indel Polymorphism rs150550023 in theCancers · 2020Article
- MDM2 inhibition in combination with endocrine therapy and CDK4/6 inhibition for the treatment of ER-positive breast cancer.Breast cancer research : BCR · 2020Article
- CircularRNA-9119 promotes the proliferation of cervical cancer cells by sponging miR-126/MDM4.Molecular and cellular biochemistry · 2020Article
- Identification of crucial aberrantly methylated and differentially expressed genes related to cervical cancer using an integrated bioinformatics analysis.Bioscience reports · 2020Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
MDM2 and MDM4 are heterodimeric, non-redundant oncoproteins that potently inhibit the p53 tumor suppressor protein. MDM2 and MDM4 also enhance the tumorigenicity of breast cancer cells in in vitro and in vivo models and are overexpressed in primary human breast cancers. Prior studies have characterized Estrogen Receptor Alpha (ERα/ESR1) as a regulator of MDM2 expression and an MDM2- and p53-interacting protein. However, similar crosstalk between ERα and MDM4 has not been investigated. Moreover, signaling pathways that mediate the overexpression of MDM4 in human breast cancer remain to be elucidated. Using the Cancer Genome Atlas (TCGA) breast invasive carcinoma patient cohort, we have analyzed correlations between ERα status and MDM4 and MDM2 expression in primary, treatment-naïve, invasive breast carcinoma samples. We report that the expression of MDM4 and MDM2 is elevated in primary human breast cancers of luminal A/B subtypes and associates with ERα-positive disease, independently of p53 mutation status. Furthermore, in cell culture models, ERα positively regulates MDM4 and MDM2 expression via p53-independent mechanisms, and these effects can be blocked by the clinically-relevant endocrine therapies fulvestrant and tamoxifen. Additionally, ERα also positively regulates p53 expression. Lastly, we report that endogenous MDM4 negatively regulates ERα expression and forms a protein complex with ERα in breast cancer cell lines and primary human breast tumor tissue. This suggests direct signaling crosstalk and negative feedback loops between ERα and MDM4 expression in breast cancer cells. Collectively, these novel findings implicate ERα as a central component of the p53-MDM2-MDM4 signaling axis in human breast cancer.
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