ArticleOncogene2010
Adenovirus 5 E1A enhances histone deacetylase inhibitors-induced apoptosis through Egr-1-mediated Bim upregulation.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- The multilayered control of acetylation during adenovirus-based immunotherapy of cancer.Molecular therapy. Oncology · 2025Review
- MRCK as a Potential Target for Claudin-Low Subtype of Breast Cancer.International journal of biological sciences · 2024Article
- Article
- The potential role of YAP in Axl-mediated resistance to EGFR tyrosine kinase inhibitors.American journal of cancer research · 2019Article
- Article
- Histone deacetylase inhibitor trichostatin A sensitises cisplatin-resistant ovarian cancer cells to oncolytic adenovirus.Oncotarget · 2018Article
- MKP1 mediates chemosensitizer effects of E1a in response to cisplatin in non-small cell lung carcinoma cells.Oncotarget · 2015Article
- AduPARE1A and gemcitabine combined treatment trigger synergistic antitumor effects in pancreatic cancer through NF-κB mediated uPAR activation.Molecular cancer · 2015Article
- E1a promotes c-Myc-dependent replicative stress: implications in glioblastoma radiosensitization.Cell cycle (Georgetown, Tex.) · 2014Article
- Elements in the Development of a Production Process for Modified Vaccinia Virus Ankara.Microorganisms · 2013Review
- Caspase-independent cell death is involved in the negative effect of EGF receptor inhibitors on cisplatin in non-small cell lung cancer cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
- Early growth response 1 regulates glucose deprivation-induced necrosis.Oncology reports · 2013Article
- Migfilin sensitizes cisplatin-induced apoptosis in human glioma cells in vitro.Acta pharmacologica Sinica · 2012Article
- Egr-1 transactivates Bim gene expression to promote neuronal apoptosis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Article
- Article
- Ras Participates in the Regulation of the Stability of Adenoviral Protein E1A via MAP-kinase ERK.Acta naturaeArticle
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Histone deacetylase inhibitors (HDACi) are potent anti-cancer agents for variety of cancer types. Suberoylanilide hydroxamic acid (SAHA) has been approved as a drug to treat cutaneous T cell lymphoma, and the combination of HDACi and other agents have been actively tested in many clinical trials. Adenovirus 5 early region 1A (E1A) has been shown to exhibit high tumor suppressor activity, and gene therapy using E1A has been tested in clinical trials. Here, we showed that proapoptotic activity of HDACi was robustly enhanced by E1A in multiple cancer cells, but not in normal cells. Moreover, we showed that combination of E1A gene therapy and SAHA showed high therapeutic efficacy with low toxicity in vivo ovarian and breast xenograft models. SAHA downregulated Bcl-XL and upregulated proapoptotic BH3-only protein Bim, whose expression was further enhanced by E1A in cancer cells. These alterations of Bcl-2 family proteins were critical for apoptosis induced by the combination in cancer cells. SAHA enhanced acetylation of histone H3 in Bim promoter region, while E1A upregulated Egr-1, which was directly involved in Bim transactivation. Together, our results provide not only a novel insight into the mechanisms underlying anti-tumor activity of E1A, but also a rationale for the combined HDACi and E1A gene therapy in future clinical trials.
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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.