title: Retinoid signaling in immortalized and carcinoma-derived human uroepithelial cells.
abstract: 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.
authors.affiliation: Department of Urology, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
authors.forename: P
authors.initials: P
authors.lastname: Waliszewski
authors.forename: M
authors.initials: M
authors.lastname: Waliszewska
authors.forename: N
authors.initials: N
authors.lastname: Gordon
authors.forename: R E
authors.initials: RE
authors.lastname: Hurst
authors.forename: D M
authors.initials: DM
authors.lastname: Benbrook
authors.forename: A
authors.initials: A
authors.lastname: Dhar
authors.forename: G P
authors.initials: GP
authors.lastname: Hemstreet
mesh_terms: 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
chemical_list: 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