Retinoid receptor mRNA expression profiles in human bladder cancer specimens.
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.
Boorjian
Stephen
S
Department of Urology, New York Presbyterian Hospital-Weill-Cornell Medical Center, 1300 York Avenue, New York, NY 10021, USA.
Scherr
Douglas S
DS
Mongan
Nigel P
NP
Zhuang
Yong
Y
Nanus
David M
DM
Gudas
Lorraine J
LJ
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D016022:Case-Control Studies; D018890:Chemoprevention; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis* / Q000235:genetics*; D012176:Retinoids / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D012176:Retinoids