ArticleThe Journal of biological chemistry2009
Rexinoid-induced expression of IGFBP-6 requires RARbeta-dependent permissive cooperation of retinoid receptors and AP-1.
Article in The Journal of biological chemistry, 2009. 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, 30 citations in OpenAlex.
- Peretinoin, an acyclic retinoid, improves the hepatic gene signature of chronic hepatitis C following curative therapy of hepatocellular carcinoma.BMC cancer · 2013Trial
- Targeting the TR4 nuclear receptor with antagonist bexarotene can suppress the proopiomelanocortin signalling in AtT-20 cells.Journal of cellular and molecular medicine · 2021Article
- Peretinoin, an Acyclic Retinoid, for the Secondary Prevention of Hepatocellular Carcinoma.Molecules (Basel, Switzerland) · 2021Review
- Translation of a Tissue-Selective Rexinoid, UAB30, to the Clinic for Breast Cancer Prevention.Current topics in medicinal chemistry · 2017Review
- Vitamin A depletion induced by cigarette smoke is associated with an increase in lung cancer-related markers in rats.Journal of biomedical science · 2015Article
- Conformationally Defined Rexinoids and Their Efficacy in the Prevention of Mammary Cancers.Journal of medicinal chemistry · 2015Article
- Retinoid roles in blocking hepatocellular carcinoma.Hepatobiliary surgery and nutrition · 2015Review
- Retinoids induce cellular senescence in breast cancer cells by RAR-β dependent and independent pathways: Potential clinical implications (Review).International journal of oncology · 2015Review
- Understanding the Key to Targeting the IGF Axis in Cancer: A Biomarker Assessment.Frontiers in oncology · 2015Review
- IGF binding proteins in cancer: mechanistic and clinical insights.Nature reviews. Cancer · 2014Review
- Advances in Preventive Therapy for Estrogen-Receptor-Negative Breast Cancer.Current breast cancer reports · 2014Review
- The combination of tamoxifen and the rexinoid LG100268 prevents ER-positive and ER-negative mammary tumors in p53-null mammary gland mice.Cancer prevention research (Philadelphia, Pa.) · 2012Article
- SLC22A5/OCTN2 expression in breast cancer is induced by estrogen via a novel intronic estrogen-response element (ERE).Breast cancer research and treatment · 2012Article
- Cancer-preventive rexinoid modulates neutral lipid contents of mammary epithelial cells through a peroxisome proliferator-activated receptor γ-dependent mechanism.Molecular pharmacology · 2012Article
- Estrogen induces c-myc gene expression via an upstream enhancer activated by the estrogen receptor and the AP-1 transcription factor.Molecular endocrinology (Baltimore, Md.) · 2011Article
- Chemoprevention of hormone receptor-negative breast cancer: new approaches needed.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2011Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The synthetic rexinoid bexarotene (Targretin, LGD1069) inhibits the formation of both estrogen receptor-negative and estrogen receptor-positive breast cancer in preclinical models and controls the expression of growth-regulatory biomarkers, such as IGFBP-6 (insulin-like growth factor-binding protein 6), RARbeta, or cyclin D1. In this study, we identified a classical retinoic acid-responsive element in the first intron in the IGFBP-6 gene adjacent to a consensus AP-1 binding site, both elements essential for rexinoid-induced expression of IGFBP-6. In chromatin binding experiments, bexarotene increased the occupancy of the identified enhancer element by RXRalpha, RARbeta, cJun, cFos, and p300. In normal mammary epithelial cells and T47D breast cancer cells, small interfering RNA-mediated knockdown of all RXR isoforms or RARbeta, but not RARalpha or RARgamma alone, blocked the induction of IGFBP-6 by bexarotene. Simultaneous knockdown of RARalpha and RARgamma abrogated both the induction of RARbeta and the up-regulation and secretion of IGFBP-6. The suppression of either RARbeta or cJun by small interfering RNA blocked the recruitment of RXRalpha and cJun to the enhancer. These results demonstrate a novel cooperative interaction between retinoid receptors and AP-1 orchestrated by RARbeta and highlight a novel mechanism by which RARbeta can mediate the cancer-preventive effects of rexinoids.
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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.