PSCA expression is regulated by phorbol ester and cell adhesion in the bladder carcinoma cell line RT112.
The expression of the surface protein prostate stem cell antigen (PSCA) in prostate carcinoma increases in parallel with the progression of the tumor. In contrast, we have recently shown that PSCA expression is reduced or undetectable in other types of undifferentiated tumors. To elucidate the cellular mechanisms that underlie this complex pattern of expression, we studied regulatory parameters for PSCA expression in the bladder carcinoma cell line RT112 by Northern analysis. PSCA gene expression was stimulated by a culture dish surface that caused aggregation of cells, suggesting that its expression is regulated by mechanisms related to the adhesion of epithelial cells. Phorbol ester markedly stimulated PSCA gene expression in a cycloheximide- and actinomycin-inhibitable manner after a lag phase of 10 h, indicating that transcription of the PSCA gene is regulated by protein kinase C and a newly synthesized protein. In contrast, epidermal growth factor, platelet-derived growth factor (PDGF)-BB, tumor necrosis factor-alpha, interferon-gamma or a slightly lowered pH failed to increase PSCA mRNA levels. Consistent with the variable expression of PSCA in different tumors, our analysis in RT112 cells shows that its expression is controlled by a strongly inducible promoter that is specifically regulated by extracellular signals.
Bahrenberg
G
G
Institute of Pharmacology and Toxicology, Medical School of the Technical University RWTH Aachen, Wendlingweg 2, D-52057, Aachen, Germany. gregor.bahrenberg@post.rwth-aachen.de
Brauers
A
A
Joost
H G
HG
Jakse
G
G
D000951:Antigens, Neoplasm; D015152:Blotting, Northern; D002448:Cell Adhesion; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism; D058851:GPI-Linked Proteins; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007371:Interferon-gamma / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010703:Phorbol Esters / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
D000951:Antigens, Neoplasm; D016207:Cytokines; D018076:DNA, Complementary; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D019384:Nucleic Acid Synthesis Inhibitors; C110843:PSCA protein, human; D010703:Phorbol Esters; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D004815:Epidermal Growth Factor; D007371:Interferon-gamma; D003513:Cycloheximide; D011493:Protein Kinase C