Daša Zupančič (Author), Jelena Korać-Prlić (Author), Mateja Erdani-Kreft (Author), Lucija Franković (Author), Katarina Vilović (Author), Jera Jeruc (Author), Rok Romih (Author), Janoš Terzić (Author)

Abstract

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.

Keywords

mehur;early carcinogenesis;vitamin A;urinary bladder;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL MF - Faculty of Medicine
UDC: 616-006
COBISS: 21184515 Link will open in a new window
ISSN: 2072-6694
Views: 191
Downloads: 62
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Other data

Secondary language: Slovenian
Secondary keywords: mehur;early carcinogenesis;vitamin A;
Type (COBISS): Article
Pages: str. 1-19
Volume: ǂVol. ǂ12
Issue: ǂiss. ǂ7
Chronology: 2020
DOI: 10.3390/cancers12071712
ID: 14075145