ArticleBreast cancer research and treatment2015
Down-regulation of programmed cell death 4 (PDCD4) is associated with aromatase inhibitor resistance and a poor prognosis in estrogen receptor-positive breast cancer.
Article in Breast cancer research and treatment, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 58 citations in OpenAlex.
- PDCD4: A Double-Edged Sword in Neurological Diseases.Molecular neurobiology · 2026Review
- Molecular Basis of Simalikalactone D Sensitivity in Triple-Negative Breast Cancer Cells.Biomolecules · 2025Article
- Article
- Atg7 senses ATP levels and regulates AKTCommunications biology · 2023Article
- Non-Coding RNAs Modulating Estrogen Signaling and Response to Endocrine Therapy in Breast Cancer.Cancers · 2023Review
- Tumor Suppressor p53 Down-Regulates Programmed Cell Death Protein 4 (PDCD4) Expression.Current oncology (Toronto, Ont.) · 2023Article
- Role of Exemestane in the Treatment of Estrogen-Receptor-Positive Breast Cancer: A Narrative Review of Recent Evidence.Advances in therapy · 2022Review
- PDCD4 Simultaneously Promotes Microglia Activation via PDCD4-MAPK-NF-κB Positive Loop and Facilitates Neuron Apoptosis During Neuroinflammation.Inflammation · 2022Article
- Dissecting the Roles of PDCD4 in Breast Cancer.Frontiers in oncology · 2022Review
- circ-NOL10 regulated by MTDH/CASC3 inhibits breast cancer progression and metastasis via multiple miRNAs and PDCD4.Molecular therapy. Nucleic acids · 2021Article
- Clinical Significance of PDCD4 in Melanoma by Subcellular Expression and in Tumor-Associated Immune Cells.Cancers · 2021Article
- miR-21a inhibits decidual cell apoptosis by targeting Pdcd4.Genes & diseases · 2021Article
- Andrographolide Suppresses the Growth and Metastasis of Luminal-Like Breast Cancer by Inhibiting the NF-κB/miR-21-5p/PDCD4 Signaling Pathway.Frontiers in cell and developmental biology · 2021Article
- Nuclear PDCD4 Expression Defines a Subset of Luminal B-Like Breast Cancers with Good Prognosis.Hormones & cancer · 2020Article
- Stat-3 signaling promotes cell proliferation and metastasis of gastric cancer through PDCD4 downregulation.The Kaohsiung journal of medical sciences · 2020Article
- Article
- Critical Role of microRNA-21 in the Pathogenesis of Liver Diseases.Frontiers in medicine · 2020Review
- Analysis of the microRNA Expression Profile of Bovine Monocyte-derived Macrophages Infected withInternational journal of molecular sciences · 2019Article
- Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions.International journal of molecular sciences · 2019Review
- Genomic alterations of Tenascin C in highly aggressive prostate cancer: a meta-analysis.Genes & cancer · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Progression or recurrence due to resistance to aromatase inhibitors (AIs) is a significant clinical problem for a considerable number of patients with breast cancer. Programmed cell death 4 (PDCD4), a tumor suppressor protein, is targeted for degradation during tumor progression. In the current study, we aimed to examine PDCD4 expression and regulation in AI-resistant breast cancer cells, and its association with survival in patients with estrogen receptor (ER)-positive breast cancer. We determined PDCD4 expression levels in AI-resistant breast cancer cell lines and ER-positive breast cancer tumors, investigated the regulation of PDCD4 in AI-resistant breast cancer cell lines, and carried out a Kaplan-Meier survival analysis in two independent cohorts that included a total of 420 patients with ER-positive breast cancer. We found that PDCD4 expression was down-regulated in AI-resistant breast cancer cells, and this down-regulation was inversely correlated with activation of HER2 signaling. Moreover, lower expression of PDCD4 was significantly associated with HER2 positive status in ER-positive breast tumors. Down-regulation of PDCD4 was mediated through up-regulation of HER2 via the mitogen-activated protein kinase (MAPK), protein kinase B (PKB/AKT), and miR-21 in AI-resistant breast cancer cells. MiR-21 inhibitor and the ER down-regulator fulvestrant induced PDCD4 expression and decreased cell proliferation in AI-resistant breast cancer cells. Furthermore, forced overexpression of PDCD4 resensitized AI-resistant cells to AI or hormone deprivation. Finally, we identified that down-regulation of PDCD4 was associated with a lower rate of disease-free survival in patients with ER-positive breast cancer and high histologic grade of breast tumors. In summary, our study shows that expression of PDCD4 is down-regulated by HER2 signaling in AI-resistant breast cancer. Down-regulation of PDCD4 is associated with AI resistance and a poor prognosis in patients with ER-positive breast cancer.
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