Bladder cancer is the tenth most common cancer in the world with a high recurrence rate. Epidemiological studies have shown that increased dietary intake of vitamin A reduces the risk of developing bladder cancer. The most important bioactive forms of vitamin A are retinol, retinaldehyde and retinoic acid. The transmembrane receptor STRA6 (stimulated by retinoic acid 6) is responsible for cellular retinol uptake. In the cell, retinol can be converted into retinyl ester for storage by the enzyme LRAT (lecithin retinol acyltransferase) or it can be converted into retinaldehyde, which is irreversibly oxidised to retinoic acid by the enzyme ALDH1/2 (aldehyde dehydrogenase). Retinoic acid binds to the protein CRABP1 (cellular retinoic acid binding protein), which transports it into the cell nucleus. The nuclear receptor for retinoic acid RXR (retinoid X receptor) activates the transcription of the target genes after the retinoic acid binds. Abnormal retinoic acid signalling is associated with carcinogenesis in several cancers, including bladder cancer. In our thesis, we investigated the expression and localisation of STRA6, LRAT, ALDH1/2, CRABP1 and RXR in samples of normal and cancerous human and rat urothelium using immunostaining and Western blot. We found differences in the expression of the proteins between normal and cancerous urothelium. STRA6 was expressed mainly in the surface cells in normal human, whereas it was expressed in all cell layers in cancerous urothelium. We detected a statistically significant increase in the amount of STRA6 in rat samples with the most advanced bladder cancer compared to normal rat urothelium. LRAT was expressed in all cell layers in both normal and cancerous human and rat samples. Quantification showed increased amount of LRAT in cancerous samples. ALDH in normal and cancerous human urothelium was predominantly present in basal and intermediate cells, except in one sample with muscle-invasive papillary urothelial carcinoma (pT2), in which the reaction was negative. In normal rat urothelium, it was strongly expressed in basal and intermediate cells, whereas it was heterogeneously expressed in cancerous rat urothelium. CRABP1 was expressed in all cell layers in normal and cancerous human urothelium, except at stage pT2, where CRABP1 was expressed only in surface cells. In the normal rat urothelium, the reaction to CRABP1 was negative, whereas it was heterogeneously expressed in the cancerous rat urothelium. Quantification showed increased amount of CRABP1 in human and rat cancerous samples, but this was not statistically significant. Experiments with RXR were only performed on human samples. RXR was expressed in the nuclei of all cell layers in both normal and cancerous urothelium. In our study, we showed differences in localisation and amount of the proteins STRA6, LRAT, ALDH1/2, CRABP1 and RXR in human and rat urothelium.
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