ArticleCell division2013
Silencing CDK4 radiosensitizes breast cancer cells by promoting apoptosis.
Article in Cell division, 2013. 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 trial behind it
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- Article
- The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review).International journal of molecular medicine · 2025Review
- Radiosensitizing effects of CDK4/6 inhibitors in hormone receptor-positive and HER2-negative breast cancer mediated downregulation of DNA repair mechanism and NF-κB-signaling pathway.Translational oncology · 2024Article
- Oxidative Stress and Cell Cycle Arrest in Seminiferous Tubules Nearby Varicose Vessels: New Perspectives from Experimental Varicocele.Reproductive sciences (Thousand Oaks, Calif.) · 2023Article
- FOXK1 regulates malignant progression and radiosensitivity through direct transcriptional activation of CDC25A and CDK4 in esophageal squamous cell carcinoma.Scientific reports · 2023Article
- CDK 4/6 inhibitors combined with radiotherapy: A review of literature.Clinical and translational radiation oncology · 2021Review
- CDK4/6 inhibitors: a novel strategy for tumor radiosensitization.Journal of experimental & clinical cancer research : CR · 2020Review
- CDK4/6 inhibitors in P16/HPV16-negative squamous cell carcinoma of the head and neck.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2020Review
- TTK promotes mesenchymal signaling via multiple mechanisms in triple negative breast cancer.Oncogenesis · 2018Article
- Abemaciclib, a Selective CDK4/6 Inhibitor, Enhances the Radiosensitivity of Non-Small Cell Lung CancerClinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- The E2F activators control multiple mitotic regulators and maintain genomic integrity through Sgo1 and BubR1.Oncotarget · 2017Article
- Comparison of Two Components of Propolis: Caffeic Acid (CA) and Caffeic Acid Phenethyl Ester (CAPE) Induce Apoptosis and Cell Cycle Arrest of Breast Cancer Cells MDA-MB-231.Molecules (Basel, Switzerland) · 2017Article
- Caffeic Acid Phenethyl Ester Increases Radiosensitivity of Estrogen Receptor-Positive and -Negative Breast Cancer Cells by Prolonging Radiation-Induced DNA Damage.Journal of breast cancer · 2016Article
- Silencing of E2F3 suppresses tumor growth of Her2+ breast cancer cells by restricting mitosis.Oncotarget · 2015Article
- CDK4-mediated MnSOD activation and mitochondrial homeostasis in radioadaptive protection.Free radical biology & medicine · 2015Article
- Combining targeted agents with modern radiotherapy in soft tissue sarcomas.Journal of the National Cancer Institute · 2014Review
- E2F activators signal and maintain centrosome amplification in breast cancer cells.Molecular and cellular biology · 2014Article
- Cyclin-dependent kinase 4 overexpression is mostly independent of gene amplification and constitutes an independent prognosticator for nasopharyngeal carcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- The other side of the coin: the tumor-suppressive aspect of oncogenes and the oncogenic aspect of tumor-suppressive genes, such as those along the CCND-CDK4/6-RB axis.Cell cycle (Georgetown, Tex.) · 2014Review
- Differential expression of centrosome regulators in Her2+ breast cancer cells versus non-tumorigenic MCF10A cells.Cell division · 2014Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe discovery of molecular markers associated with various breast cancer subtypes has greatly improved the treatment and outcome of breast cancer patients. Unfortunately, breast cancer cells acquire resistance to various therapies. Mounting evidence suggests that resistance is rooted in the deregulation of the G1 phase regulatory machinery.
methodsTo address whether deregulation of the G1 phase regulatory machinery contributes to radiotherapy resistance, the MCF10A immortalized human mammary epithelial cell line, ER-PR-Her2+ and ER-PR-Her2- breast cancer cell lines were irradiated. Colony formation assays measured radioresistance, while immunocytochemistry, Western blots, and flow cytometry measured the cell cycle, DNA replication, mitosis, apoptosis, and DNA breaks.
resultsMolecular markers common to all cell lines were overexpressed, including cyclin A1 and cyclin D1, which impinge on CDK2 and CDK4 activities, respectively. We addressed their potential role in radioresistance by generating cell lines stably expressing small hairpin RNAs (shRNA) against CDK2 and CDK4. None of the cell lines knocked down for CDK2 displayed radiosensitization. In contrast, all cell lines knocked down for CDK4 were significantly radiosensitized, and a CDK4/CDK6 inhibitor sensitized MDA-MB-468 to radiation induced apoptosis. Our data showed that silencing CDK4 significantly increases radiation induced cell apoptosis in cell lines without significantly altering cell cycle progression, or DNA repair after irradiation. Our results indicate lower levels of phospho-Bad at ser136 upon CDK4 silencing and ionizing radiation, which has been shown to signal apoptosis.
conclusionBased on our data we conclude that knockdown of CDK4 activity sensitizes breast cancer cells to radiation by activating apoptosis pathways.
Identifiers
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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.