ArticleOncotarget2017
Estrogen-activated MDM2 disrupts mammary tissue architecture through a p53-independent pathway.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Murine double minute 2 (MDM2) as an appealing target for natural products in cancer treatment.Molecular biology reports · 2026Review
- 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
- A cancer persistent DNA repair circuit driven by MDM2, MDM4 (MDMX), and mutant p53 for recruitment of MDC1 and 53BP1 on chromatin.Nucleic acids research · 2025Article
- Chemokine CXCL12 Activates CXC Receptor 4 Metastasis Signaling Through the Upregulation of a CXCL12/CXCR4/MDMX (MDM4) Axis.Cancers · 2024Article
- The Evolving Pathways of the Efficacy of and Resistance to CDK4/6 Inhibitors in Breast Cancer.Cancers · 2023Review
- Targeting Breast Cancer: The Familiar, the Emerging, and the Uncharted Territories.Biomolecules · 2023Review
- MDM2- an indispensable player in tumorigenesis.Molecular biology reports · 2023Review
- Review
- Novel genomic alteration in superficial esophageal squamous cell neoplasms in non-smoker non-drinker females.Scientific reports · 2021Article
- The roles and regulation of MDM2 and MDMX: it is not just about p53.Genes & development · 2021Review
- Role of Sex in the Therapeutic Targeting of p53 Circuitry.Frontiers in oncology · 2021Review
- Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.Frontiers in oncology · 2021Review
- Tumor suppressor OTUD3 induces growth inhibition and apoptosis by directly deubiquitinating and stabilizing p53 in invasive breast carcinoma cells.BMC cancer · 2020Article
- c-Myc induced the regulation of long non-coding RNA RHPN1-AS1 on breast cancer cell proliferation via inhibiting P53.Molecular genetics and genomics : MGG · 2019Article
- Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: A review.International journal of cancer · 2019Review
- Analysis of gene co‑expression network reveals prognostic significance of CNFN in patients with head and neck cancer.Oncology reports · 2019Article
- MDM2, MDM2-C, and mutant p53 expression influence breast cancer survival in a multiethnic population.Breast cancer research and treatment · 2019Article
- Context-dependent roles of MDMX (MDM4) and MDM2 in breast cancer proliferation and circulating tumor cells.Breast cancer research : BCR · 2019Article
- The Role of MDM2 in Promoting Genome Stability versus Instability.International journal of molecular sciences · 2017Review
- HAX-1 Protects Glioblastoma Cells from Apoptosis through the Akt1 Pathway.Frontiers in cellular neuroscience · 2017Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
The Cancer Genome Atlas (TCGA) data indicate that high MDM2 expression correlates with all subtypes of breast cancer. Overexpression of MDM2 drives breast oncogenesis in the presence of wild-type or mutant p53 (mtp53). Importantly, estrogen-receptor positive (ER+) breast cancers overexpress MDM2 and estrogen mediates this expression. We previously demonstrated that this estrogen-MDM2 axis activates the proliferation of breast cancer cell lines T47D (mtp53 L194F) and MCF7 (wild-type p53) in a manner independent of increased degradation of wild-type p53 (ie, p53-independently). Herein we present data supporting the role of the estrogen-MDM2 axis in regulating cell proliferation and mammary tissue architecture of MCF7 and T47D cells in a p53-independent manner. Inducible shRNA mediated MDM2 knockdown inhibited colony formation in soft agar, decreased mass size and induced lumen formation in matrigel and also significantly reduced mitosis as seen by decreased phospho-histone H3 positive cells. The knockdown of MDM2 in both cell lines decreased Rb phosphorylation and the level of E2F1 protein. This signaling was through the estrogen receptor because fulvestrant (a selective estrogen receptor degrader) decreased MDM2 protein levels and decreased phosphorylation of Rb. Taken together these data indicate that in some ER+ breast cancers the estrogen-MDM2-Rb-E2F1 axis is a central hub for estrogen-mediated p53-independent signal transduction. This is the first indication that estrogen signaling utilizes the estrogen-MDM2 axis to provoke phosphorylation of Rb and increase E2F1 while promoting abnormal mammary architecture.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.