Many melanoma cells are resistant to the anti-proliferative effect of all trans retinoic acid (ATRA). Retinoic Acid Receptor-beta2 (RAR-beta2) mediates the ATRA growth inhibition. We found a correlation between the anti-proliferative activity of ATRA and expression of RAR-beta2. There was not a strict correlation between DNA methylation of RAR-beta gene and its expression. There was no difference in global and RARbeta specific nucleosome repeat length (NRL) in melanoma and melanocytes or between control and ATRA treated cells. Pan-acetylation of H3 and H4 within the RAR-beta gene promoter was higher in cells expressing RAR-beta2. All trans retinoic acid treatment of responsive cells did not change pan-acetylation of H3/H4, but addition of ATRA to non-responsive cells increased H4 pan-acetylation. Phytochemicals or the histone deacetylase inhibitor Trichostatin A did not restore expression of RAR-beta2. Treatment of WM1366 melanoma cells with 5-aza 2'-deoxycytidine reactivated RAR-beta2 gene expression and restored the ability of ATRA to further induce the expression of this gene. Therefore, promoter methylation is responsible for silencing of RAR-beta2 in some melanoma cells and pan-acetylation of H3 likely plays a permissive role in expression of RAR-beta2.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/j.1755-148X.2010.00702.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Retinoids and retinoid-binding proteins: Unexpected roles in metabolic disease.
Curr Top Dev Biol
January 2025
Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, Case Western Reserve University, Cleveland, OH, United States.
Alterations in tissue expression levels of both retinol-binding protein 2 (RBP2) and retinol-binding protein 4 (RBP4) have been associated with metabolic disease, specifically with obesity, glucose intolerance and hepatic steatosis. Our laboratories have shown that this involves novel pathways not previously considered as possible linkages between impaired retinoid metabolism and metabolic disease development. We have established both biochemically and structurally that RBP2 binds with very high affinity to very long-chain unsaturated 2-monoacylglycerols like the canonical endocannabinoid 2-arachidonoyl glycerol (2-AG) and other endocannabinoid-like substances.
View Article and Find Full Text PDFMeiosis and retinoic acid in the mouse fetal gonads: An unforeseen twist.
Curr Top Dev Biol
January 2025
Université de Strasbourg, IGBMC UMR 7104, Illkirch, France; CNRS, UMR 7104, Illkirch, France; Inserm, UMR-S 1258, Illkirch, France; IGBMC, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France. Electronic address:
In mammals, differentiation of germ cells is crucial for sexual reproduction, involving complex signaling pathways and environmental cues defined by the somatic cells of the gonads. This review examines the long-standing model positing that all-trans retinoic acid (ATRA) acts as a meiosis-inducing substance (MIS) in the fetal ovary by inducing expression of STRA8 in female germ cells, while CYP26B1 serves as a meiosis-preventing substance (MPS) in the fetal testis by degrading ATRA and preventing STRA8 expression in the male germ cells until postnatal development. Recent genetic studies in the mouse challenge this paradigm, revealing that meiosis initiation in female germ cells can occur independently of ATRA signaling, with key roles played by other intrinsic factors like DAZL and DMRT1, and extrinsic signals such as BMPs and vitamin C.
View Article and Find Full Text PDFMultiple roles for retinoid signaling in craniofacial development.
Curr Top Dev Biol
January 2025
Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, United States. Electronic address:
Retinoic acid (RA) signaling plays multiple essential roles in development of the head and face. Animal models with mutations in genes involved in RA signaling have enabled understanding of craniofacial morphogenic processes that are regulated by the retinoid pathway. During craniofacial morphogenesis RA signaling is active in spatially restricted domains defined by the expression of genes involved in RA production and RA breakdown.
View Article and Find Full Text PDFVitamin A supply in the eye and establishment of the visual cycle.
Curr Top Dev Biol
January 2025
Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH, United States. Electronic address:
Animals perceiving light through visual pigments have evolved pathways for absorbing, transporting, and metabolizing the precursors essential for synthesis of their retinylidene chromophores. Over the past decades, our understanding of this metabolism has grown significantly. Through genetic manipulation, researchers gained insights into the metabolic complexity of the pathways mediating the flow of chromophore precursors throughout the body, and their enrichment within the eyes.
View Article and Find Full Text PDFRetinoid signaling in pancreas development, islet function, and disease.
Curr Top Dev Biol
January 2025
University of Michigan, Department of Pharmacology, Caswell Diabetes Institute, Ann Arbor, MI, United States. Electronic address:
All-trans retinoic acid (ATRA) signaling is essential in numerous different biological contexts. This review highlights the diverse roles of ATRA during development, function, and diseases of the pancreas. ATRA is essential to specify pancreatic progenitors from gut tube endoderm, endocrine and exocrine differentiation, and adult islet function.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!