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Open AccessArticle

Vitamin A Rich Diet Diminishes Early Urothelial Carcinogenesis by Altering Retinoic Acid Signaling

1
Institute of Cell Biology, Faculty of Medicine, University of Ljubljana,1000 Ljubljana, Slovenia
2
Laboratory for Cancer Research, School of Medicine, University of Split, 21000 Split, Croatia
3
Department of Pathology, University Hospital of Split, 21000 Split, Croatia
4
Institute of Pathology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(7), 1712; https://doi.org/10.3390/cancers12071712
Received: 23 April 2020 / Revised: 17 June 2020 / Accepted: 18 June 2020 / Published: 28 June 2020
(This article belongs to the Section Molecular Cancer Biology)
Urinary bladder cancer is one of the leading malignancies worldwide, with the highest recurrence rates. A diet rich in vitamin A has proven to lower the risk of cancer, yet the molecular mechanisms underlying this effect are unknown. We found that vitamin A decreased urothelial atypia and apoptosis during early bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Vitamin A did not alter urothelial cell desquamation, differentiation, or proliferation rate. Genes like Wnt5a, involved in retinoic acid signaling, and transcription factors Pparg, Ppara, Rxra, and Hoxa5 were downregulated, while Sox9 and Stra6 were upregulated in early urothelial carcinogenesis. When a vitamin A rich diet was provided during BBN treatment, none of these genes was up- or downregulated; only Lrat and Neurod1 were upregulated. The lecithin retinol acyltransferase (LRAT) enzyme that produces all-trans retinyl esters was translocated from the cytoplasm to the nuclei in urothelial cells as a consequence of BBN treatment regardless of vitamin A rich diet. A vitamin A-rich diet altered retinoic acid signaling, decreased atypia and apoptosis of urothelial cells, and consequently diminished early urothelial carcinogenesis. View Full-Text
Keywords: urinary bladder; early carcinogenesis; vitamin A; retinoic acid signaling; apoptosis urinary bladder; early carcinogenesis; vitamin A; retinoic acid signaling; apoptosis
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MDPI and ACS Style

Zupančič, D.; Korać-Prlić, J.; Kreft, M.E.; Franković, L.; Vilović, K.; Jeruc, J.; Romih, R.; Terzić, J. Vitamin A Rich Diet Diminishes Early Urothelial Carcinogenesis by Altering Retinoic Acid Signaling. Cancers 2020, 12, 1712.

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