ArticleMolecular and cellular biology2005
Impaired retinoic acid (RA) signal leads to RARbeta2 epigenetic silencing and RA resistance.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Pooled it
- Effects of RARα ligand binding domain mutations on breast fibroepithelial tumor function and signaling.NPJ breast cancer · 2025Article
- Combining phenotypic profiling and targeted RNA-Seq reveals linkages between transcriptional perturbations and chemical effects on cell morphology: Retinoic acid as an example.Toxicology and applied pharmacology · 2022Article
- Super-enhancer associated core regulatory circuits mediate susceptibility to retinoic acid in neuroblastoma cells.Frontiers in cell and developmental biology · 2022Article
- Profound gene expression changes in the epithelial monolayer of active ulcerative colitis and Crohn's disease.PloS one · 2022Article
- Review
- Impact of inflammation and immunotherapy in renal cell carcinoma.Oncology letters · 2020Review
- Review
- MiR-30a and miR-379 modulate retinoic acid pathway by targeting DNA methyltransferase 3B in oral cancer.Journal of biomedical science · 2020Article
- Article
- Enhancement of tumor suppressor RAR-β protein expression by cationic liposomal-ATRA treatment in benzo(a)pyrene-induced lung cancer mice model.Naunyn-Schmiedeberg's archives of pharmacology · 2019Article
- 3D Mammary Epithelial Cell Models: A Goldmine of DCIS Biomarkers and Morphogenetic Mechanisms.Cancers · 2019Article
- Why Differentiation Therapy Sometimes Fails: Molecular Mechanisms of Resistance to Retinoids.International journal of molecular sciences · 2018Review
- Retinoic acid inhibits white adipogenesis by disrupting GADD45A-mediated Zfp423 DNA demethylation.Journal of molecular cell biology · 2017Article
- Retinoic acid induces white adipose tissue browning by increasing adipose vascularity and inducing beige adipogenesis of PDGFRαCell discovery · 2017Article
- Article
- Beyond transcription factors: how oncogenic signalling reshapes the epigenetic landscape.Nature reviews. Cancer · 2016Review
- Aldehyde dehydrogenase as a marker and functional mediator of metastasis in solid tumors.Clinical & experimental metastasis · 2016Review
- Cancer development, progression, and therapy: an epigenetic overview.International journal of molecular sciences · 2013Review
- Molecular pathways: current role and future directions of the retinoic acid pathway in cancer prevention and treatment.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to the growth-inhibitory action of retinoic acid (RA), the bioactive derivative of vitamin A, is common in human tumors. One form of RA resistance has been associated with silencing and hypermethylation of the retinoic acid receptor beta2 gene (RARbeta2), an RA-regulated tumor suppressor gene. The presence of an epigenetically silent RARbeta2 correlates with lack of the RA receptor alpha (RARalpha). Normally, RARalpha regulates RARbeta2 transcription by mediating dynamic changes of RARbeta2 chromatin in the presence and absence of RA. Here we show that interfering with RA signal through RARalpha (which was achieved by use of a dominant-negative RARalpha, by downregulation of RARalpha by RNA interference, and by use of RARalpha antagonists) induces an exacerbation of the repressed chromatin status of RARbeta2 and leads to RARbeta2 transcriptional silencing. Further, we demonstrate that RARbeta2 silencing causes resistance to the growth-inhibitory effect of RA. Apparently, RARbeta2 silencing can also occur in the absence of DNA methylation. Conversely, we demonstrate that restoration of RA signal at a silent RARbeta2 through RARalpha leads to RARbeta2 reactivation. This report provides proof of principle that RARbeta2 silencing and RA resistance are consequent to an impaired integration of RA signal at RARbeta2 chromatin.
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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.