ArticleThe Journal of clinical investigation2010
TGF-beta1-induced expression of human Mdm2 correlates with late-stage metastatic breast cancer.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 130 citations in OpenAlex.
- Opportunities in cancer gene therapy: inhibiting MDM2 and restoring p14ARF as a means to activate p53.Molecular and cellular biochemistry · 2026Review
- The miR-16-1-3p suppresses proliferation and invasiveness via the MDM2-p53 axis in TGF-β1 signaling in osteosarcoma.Molecular therapy. Oncology · 2026Article
- Non-small cell lung cancer map and analysis: exploring interconnected oncogenic signal integrators.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Targeting MDM2-p53 interaction for breast cancer therapy.Oncology research · 2025Review
- Induction of the Mdm2 gene and protein by kinase signaling pathways is repressed by the pVHL tumor suppressor.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Comprehensive molecular interaction map of TGFβ induced epithelial to mesenchymal transition in breast cancer.NPJ systems biology and applications · 2024Article
- MDM2: current research status and prospects of tumor treatment.Cancer cell international · 2024Review
- Advancements in MDM2 inhibition: Clinical and pre-clinical investigations of combination therapeutic regimens.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Review
- MDM2- an indispensable player in tumorigenesis.Molecular biology reports · 2023Review
- Review
- Article
- Association of the TGFβ gene family with microenvironmental features of gastric cancer and prediction of response to immunotherapy.Frontiers in oncology · 2022Article
- Crosslink between p53 and metastasis: focus on epithelial-mesenchymal transition, cancer stem cell, angiogenesis, autophagy, and anoikis.Molecular biology reports · 2021Review
- Fluorine-18 Labeling of the MDM2 Inhibitor RG7388 for PET Imaging: Chemistry and Preliminary Evaluation.Molecular pharmaceutics · 2021Article
- SOHO State of the Art Updates and Next Questions: Identifying and Treating "Progression" in Myelofibrosis.Clinical lymphoma, myeloma & leukemia · 2021Review
- Curcumin: Modulator of Key Molecular Signaling Pathways in Hormone-Independent Breast Cancer.Cancers · 2021Review
- The Role of TGF-Evidence-based complementary and alternative medicine : eCAM · 2021Review
- A p53-Dependent Checkpoint Induced upon DNA Damage Alters Cell Fate during hiPSC Differentiation.Stem cell reports · 2020Article
- Involvement of the TGF-β1 pathway in caveolin-1-associated regulation of head and neck tumor cell metastasis.Oncology letters · 2020Article
- MiR-135-5p inhibits TGF-β-induced epithelial-mesenchymal transition and metastasis by targeting SMAD3 in breast cancer.Journal of Cancer · 2020Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
The E3 ubiquitin ligase human murine double minute (HDM2) is overexpressed in 40%-80% of late-stage metastatic cancers in the absence of gene amplification. Hdm2 regulates p53 stability via ubiquitination and has also been implicated in altering the sensitivity of cells to TGF-beta1. Whether TGF-beta1 signaling induces Hdm2 expression leading to HDM2-mediated destabilization of p53 has not been investigated. In this study, we report that TGF-beta1-activated SMA- and MAD3 (Smad3/4) transcription factors specifically bound to the second promoter region of HDM2, leading to increased HDM2 protein expression and destabilization of p53 in human cancer cell lines. Additionally, TGF-beta1 expression led to Smad3 activation and murine double minute 2 (Mdm2) expression in murine mammary epithelial cells during epithelial-to-mesenchymal transition (EMT). Furthermore, histological analyses of human breast cancer samples demonstrated that approximately 65% of late-stage carcinomas were positive for activated Smad3 and HDM2, indicating a strong correlation between TGF-beta1-mediated induction of HDM2 and late-stage tumor progression. Identification of Hdm2 as a downstream target of TGF-beta1 represents a critical prosurvival mechanism in cancer progression and provides another point for therapeutic intervention in late-stage cancer.
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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.