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 RARalpha, RARbeta2, RARgamma and RXRalpha, as well as two putative RARbeta2 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 RARalpha, RARbeta2, RARgamma and RXRalpha
mRNA was detected in all of the non-neoplastic patient bladder specimens. RARbeta2
mRNA expression was undetectable in 7/13
tumors, RARalpha in 3/13, RARgamma in 1/13 and RXRalpha 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 RARbeta2 independent of
retinoid exposure; in three cell lines RARbeta2 expression was induced by
retinoids. RARalpha, RARgamma and RXRalpha
mRNA expression was detected in 5/5 cell lines, independent of
retinoid exposure. We found a reduction in
retinoid receptor
mRNA expression, particularly for RARbeta2, in human
bladder cancer specimens. We also demonstrated induction of RARbeta2
mRNA expression in some of the
retinoid-treated
bladder cancer cell lines. We suggest that restoration of RARbeta2 expression may be a reasonable
biomarker for developing
bladder cancer preventive and/or therapeutic drugs.