Retinoids, which include vitamin A (retinol) and its derivatives, have previously been investigated as potential chemopreventive and chemotherapeutic agents in bladder cancer. We examined mRNA expression of the retinoid receptors RARα, RARβ2, RARγ and RXRα, as well as two putative RARβ2 target genes, DAB2 and Midkine, in normal and malignant bladder tissue specimens from human patients. We evaluated 24 normal and malignant bladder specimens for retinoid receptor, DAB2 and Midkine mRNA expression using RT-PCR. We also examined the effects of retinoic acid and retinol on the expression of these genes in five human bladder cancer cell lines. Expression of RARα, RARβ2, RARγ and RXRα mRNA was detected in all of the non-neoplastic patient bladder specimens. RARβ2 mRNA expression was undetectable in 7/13 tumors, RARα in 3/13, RARγ in 1/13 and RXRα in 2/13. DAB2 mRNA was expressed in all non-neoplastic and all tumor specimens, while Midkine mRNA was detected in 8/11 non-neoplastic specimens versus 11/13 tumors. Two of the five bladder cancer cell lines expressed RARβ2 independent of retinoid exposure; in three cell lines RARβ2 expression was induced by retinoids. RARα, RARγ and RXRα mRNA expression was detected in 5/5 cell lines, independent of retinoid exposure. We found a reduction in retinoid receptor mRNA expression, particularly for RARβ2, in human bladder cancer specimens. We also demonstrated induction of RARβ2 mRNA expression in some of the retinoid-treated bladder cancer cell lines. We suggest that restoration of RARβ2 expression may be a reasonable biomarker for developing bladder cancer preventive and/or therapeutic drugs.

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