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• W2034696212 endingPage "329" @default.
• W2034696212 startingPage "315" @default.
• W2034696212 abstract "The beta-catenin signaling pathway is dysregulated in most cases of colon cancer resulting in an accumulation of nuclear beta-catenin and increased transcription of genes involved in tumor progression. This study examines the effect of retinol on beta-catenin protein levels in three all-trans retinoic acid (ATRA)-resistant human colon cancer cell lines: HCT-116, WiDr, and SW620. Each cell line was treated with increasing concentrations of retinol for 24 or 48 h. Retinol reduced beta-catenin protein levels and increased ubiquitinated beta-catenin in all cell lines. Treatment with the proteasomal inhibitor MG132 blocked the retinol-induced decrease in beta-catenin indicating retinol decreases beta-catenin by increasing proteasomal degradation. Multiple pathways direct beta-catenin to the proteasome for degradation including a p53/Siah-1/adenomatous polyposis coli (APC), a Wnt/glycogen synthase kinase-3beta/APC, and a retinoid X receptor (RXR)-mediated pathway. Due to mutations in beta-catenin (HCT-116), APC (SW620), and p53 (WiDr), only the RXR-mediated pathway remains functional in each cell line. To determine if RXRs facilitate beta-catenin degradation, cells were treated with the RXR pan-antagonist, PA452, or transfected with RXRalpha small interfering RNA (siRNA). The RXR pan-antagonist and RXRalpha siRNA reduced the ability of retinol to decrease beta-catenin protein levels. Nuclear beta-catenin induces gene transcription via interaction with T cell factor/lymphoid enhancer factor (TCF/LEF) proteins. Retinol treatment decreased the transcription of a TOPFlash reporter construct and mRNA levels of the endogenous beta-catenin target genes, cyclin D1 and c-myc. These results indicate that retinol may reduce colon cancer cell growth by increasing the proteasomal degradation of beta-catenin via a mechanism potentially involving RXR." @default.
• W2034696212 created "2016-06-24" @default.
• W2034696212 creator A5008521807 @default.
• W2034696212 creator A5019193712 @default.
• W2034696212 date "2007-01-01" @default.
• W2034696212 modified "2023-09-26" @default.
• W2034696212 title "Retinol decreases β-catenin protein levels in retinoic acid-resistant colon cancer cell lines" @default.
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• W2034696212 doi "https://doi.org/10.1002/mc.20280" @default.
• W2034696212 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17219422" @default.
• W2034696212 hasPublicationYear "2007" @default.
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