ArticleCancer biology & therapy2009
Prevention of KLF4-mediated tumor initiation and malignant transformation by UAB30 rexinoid.
Article in Cancer biology & therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 26 citations in OpenAlex.
- A Randomized, Placebo-Controlled, Double-Blind, Dose Escalation, Single Dose, and Steady-State Pharmacokinetic Study of 9cUAB30 in Healthy Volunteers.Cancer prevention research (Philadelphia, Pa.) · 2019Trial
- The retinoid X receptor agonist, 9-cis UAB30, inhibits cutaneous T-cell lymphoma proliferation through the SKP2-p27kip1 axis.Journal of dermatological science · 2018Article
- Translation of a Tissue-Selective Rexinoid, UAB30, to the Clinic for Breast Cancer Prevention.Current topics in medicinal chemistry · 2017Review
- Preclinical Evaluation of UAB30 in Pediatric Renal and Hepatic Malignancies.Molecular cancer therapeutics · 2016Article
- Article
- Retinoid X Receptor Agonists Upregulate Genes Responsible for the Biosynthesis of All-Trans-Retinoic Acid in Human Epidermis.PloS one · 2016Article
- Conformationally Defined Rexinoids and Their Efficacy in the Prevention of Mammary Cancers.Journal of medicinal chemistry · 2015Article
- Preclinical Evaluation of a Novel RXR Agonist for the Treatment of Neuroblastoma.Molecular cancer therapeutics · 2015Article
- Augmented miR-10b expression associated with depressed expression of its target gene KLF4 involved in gastric carcinoma.International journal of clinical and experimental pathology · 2015Article
- Methyl substitution of a rexinoid agonist improves potency and reveals site of lipid toxicity.Journal of medicinal chemistry · 2014Article
- Defining the communication between agonist and coactivator binding in the retinoid X receptor α ligand binding domain.The Journal of biological chemistry · 2014Article
- Methyl-substituted conformationally constrained rexinoid agonists for the retinoid X receptors demonstrate improved efficacy for cancer therapy and prevention.Bioorganic & medicinal chemistry · 2014Article
- Nuclear hormone receptor functions in keratinocyte and melanocyte homeostasis, epidermal carcinogenesis and melanomagenesis.FEBS letters · 2013Review
- The retinoid X receptors and their ligands.Biochimica et biophysica acta · 2012Review
- A KLF4-miRNA-206 autoregulatory feedback loop can promote or inhibit protein translation depending upon cell context.Molecular and cellular biology · 2011Article
- A pilot, first-in-human, pharmacokinetic study of 9cUAB30 in healthy volunteers.Cancer prevention research (Philadelphia, Pa.) · 2010Article
- Retinoid pathway and cancer therapeutics.Advanced drug delivery reviews · 2010Review
- Mammalian Krüppel-like factors in health and diseases.Physiological reviews · 2010Review
- Epithelial transformation by KLF4 requires Notch1 but not canonical Notch1 signaling.Cancer biology & therapy · 2009Article
- Expression and Function of Kruppel Like-Factors (KLF) in Carcinogenesis.Current genomics · 2009Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
The transcription factor KLF4 acts in post-mitotic epithelial cells to promote differentiation and functions in a context-dependent fashion as an oncogene. In the skin KLF4 is co-expressed with the nuclear receptors RARgamma and RXRalpha, and formation of the skin permeability barrier is a shared function of these three proteins. We utilized a KLF4-transgenic mouse model of skin cancer in combination with cultured epithelial cells to examine functional interactions between KLF4 and retinoic acid receptors. In cultured cells, activation of a conditional, KLF4-estrogen receptor fusion protein by 4-hydroxytamoxifen resulted in rapid upregulation of transcripts for nuclear receptors including RARgamma and RXRalpha. We tested retinoids in epithelial cell transformation assays, including an RAR-selective agonist (all-trans RA), an RXR-selective agonist (9-cis UAB30, rexinoid), and a pan agonist (9-cis RA). Unlike for several other genes, transformation by KLF4 was inhibited by each retinoid, implicating distinct nuclear receptor heterodimers as modulators of KLF4 transforming activity. When RXRalpha expression was suppressed by RNAi in cultured cells, transformation was promoted and the inhibitory effect of 9-cis UAB30 was attenuated. Similarly as shown for other mouse models of skin cancer, rexinoid prevented skin tumor initiation resulting from induction of KLF4 in basal keratinocytes. Rexinoid permitted KLF4 expression and KLF4-induced cell cycling, but attenuated the KLF4-induced misexpression of cytokeratin 1 in basal cells. Neoplastic lesions including hyperplasia, dysplasia and squamous cell carcinoma-like lesions were prevented for up to 30 days. Taken together, the results identify retinoid receptors including RXRalpha as ligand-dependent inhibitors of KLF4-mediated transformation or tumorigenesis.
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What OpenQuestion holds
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.