Genes related to growth and invasiveness are repressed by sodium butyrate in ovarian carcinoma cells.
Down-regulation of oncogene expression is one of the hallmarks of the process whereby transformed cells are forced into differentiation and/or growth arrest by potent inducers and therefore can represent an interim end point in cancer treatment. The differentiation inducer sodium butyrate (NaB) arrested growth of N.1 ovarian carcinoma cells and repressed expression of cyclin D1/prad1 and the invasiveness-related protease plasminogen activator-urokinase (plau). This was accompanied by the acquisition of a differentiated morphology, all of which characteristics were maintained as long as N.1 cells were exposed to the inducer. In accordance with a differentiated phenotype was the finding that fibronectin expression was increased significantly. Recently, it was shown that NaB represses the transcription factor c-myc by blocking Ca2+ signals and modulating serine threonine kinase activity. We wanted to investigate NaB-mediated interference on signals contributing to the expression on prad1, plau and growth arrest-specific 6 (gas6). Protein kinase A (PKA) inactivation de-repressed prad1 and plau transcript levels. NaB had onlygeneral but no specific influence on PKA-modulated prad1 and plau expression however. Protein kinase C activation up-regulated plau transcript levels, but not that of prad1. Prad1 expression seemed to depend on Ca2+-triggered signals. Constitutive plau expression was insensitive to additional Ca2+-mediated signals, but it became responsive upon NaB treatment.
Krupitza
G
G
Institute of Clinical Pathology, University of Vienna, Austria.
Grill
S
S
Harant
H
H
Hulla
W
W
Szekeres
T
T
Huber
H
H
Dittrich
C
C
D000262:Adenylyl Cyclases / Q000378:metabolism; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019938:Cyclin D1; D016213:Cyclins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007546:Isoquinolines / Q000494:pharmacology; D009361:Neoplasm Invasiveness / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D009857:Oncogenes / Q000187:drug effects*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics; D000099255:Growth Arrest-Specific Protein 6
D000262:Adenylyl Cyclases; D002087:Butyrates; D020148:Butyric Acid; D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases; D019938:Cyclin D1; D016213:Cyclins; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D007546:Isoquinolines; D015513:Oncogene Proteins; D011493:Protein Kinase C; D011506:Proteins; D012333:RNA, Messenger; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate; D014568:Urokinase-Type Plasminogen Activator; D000099255:Growth Arrest-Specific Protein 6; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide