Retinoid signaling in immortalized and carcinoma-derived human uroepithelial cells.
This paper investigates the presence and functionality of retinoid signaling pathways in human urinary bladder carcinoma and SV40-immortalized uroepithelial cell lines. Only two of eight cell lines were proliferation-inhibited by 10 microM of either all-trans or 13-cis-retinoic acid. Transactivation of the CAT gene under control of a retinoid-responsive element demonstrated functionality of the signaling pathway in both sensitive cell lines and four of six resistant cell lines. Relative RT-PCR analysis of a panel of retinoid-responsive and inducible genes demonstrated changes in expression levels of all the genes in response to-retinoic acid treatment together with numerous aberrations dysregulations. We conclude that retinoid signaling may be a target for inactivation during tumorigenesis by uncoupling gene expression, proliferation and differentiation. Therefore retinoids are more likely to be effective for chemoprevention than for treatment of bladder carcinomas.
Waliszewski
P
P
Department of Urology, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Waliszewska
M
M
Gordon
N
N
Hurst
R E
RE
Benbrook
D M
DM
Dhar
A
A
Hemstreet
G P
GP
D017209:Apoptosis; D002461:Cell Line, Transformed; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D006801:Humans; D010212:Papilloma; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D012176:Retinoids / Q000633:toxicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013539:Simian virus 40; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms; D019459:Urothelium / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D000097768:Retinoic Acid Receptor gamma
D015500:Chloramphenicol O-Acetyltransferase; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D012176:Retinoids; D000097768:Retinoic Acid Receptor gamma; C000607071:RARA protein, human; C082925:retinoic acid receptor beta