ArticleOncotarget2014
Oncogene-triggered suppression of DNA repair leads to DNA instability in cancer.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 1 citations in OpenAlex.
- Wogonin inhibits radiation-induced DNA damage repair in hepatocellular carcinoma cells by upregulating p21.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- Transcriptional and functional regulation of cell cycle and UV response by PPARβ in human skin epidermal cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Cytoplasmic proteotoxicity regulates HRI-dependent phosphorylation of eIF2α via the Hsp70-Bag3 module.iScience · 2022Article
- Article
- Multiple functions of p21 in cancer radiotherapy.Journal of cancer research and clinical oncology · 2021Review
- The STRIPAK Complex Regulates Response to Chemotherapy Through p21 and p27.Frontiers in cell and developmental biology · 2020Article
- The Role of the Cyclin Dependent Kinase Inhibitor p21Cancers · 2019Review
- Stromal PTEN determines mammary epithelial response to radiotherapy.Nature communications · 2018Article
- The Damaging Effect of Passenger Mutations on Cancer Progression.Cancer research · 2017Article
- FIGNL1 is overexpressed in small cell lung cancer patients and enhances NCI-H446 cell resistance to cisplatin and etoposide.Oncology reports · 2017Article
- Ionizing Radiation-Induced Endothelial Cell Senescence and Cardiovascular Diseases.Radiation research · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
DNA instability is an important contributor to cancer development. Previously, defects in the chromosome segregation and excessive DNA double strand breaks due to the replication or oxidative stresses were implicated in DNA instability in cancer. Here, we demonstrate that DNA instability can directly result from the oncogene-induced senescence signaling. Expression of the activated form of Her2 oncogene, NeuT, in immortalized breast epithelial cells led to downregulation of the major DNA repair factor histone H2AX and a number of other components of the HR and NHEJ double strand DNA breaks repair pathways. H2AX expression was regulated at the transcriptional level via a senescence pathway involving p21-mediated regulation of CDK and Rb1. The p21-dependent downregulation of H2AX was seen both in cell culture and the MMTV-neu mouse model of Her2-positive breast cancer. Importantly, downregulation of H2AX upon Her2/NeuT expression impaired repair of double strand DNA breaks. This impairment resulted in both increased DNA instability in the form of somatic copy number alterations, and in increased sensitivity to the chemotherapeutic drug doxorubicin. Overall, these findings indicate that the Her2/NeuT oncogene signaling directly potentiates DNA instability and increases sensitivity to DNA damaging treatments.
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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.