Molecular analysis of sodium butyrate-induced growth arrest.
Sodium butyrate has been shown to exert dramatic effects on the growth of cells in culture. It inhibits DNA synthesis, arrests actively proliferating cells in G1 and induces differentiation. The mechanism responsible for these various anti-proliferative effects is presently unknown. We wished to study the effects of sodium butyrate on cell growth at the molecular level, by analyzing the pattern of expression exhibited by several growth-associated genes (e.g., c-fos, c-myc, p53 and thymidine kinase) in Swiss 3T3 cells following treatment with sodium butyrate. Our results suggest that sodium butyrate-induced growth arrest of Swiss 3T3 cells (1) can be distinguished at a molecular level from the arrest brought about by other means of growth arrest; (2) does not result from a generalized mechanism which non-specifically shuts down the expression of growth-associated genes but rather occurs via a more specific mechanism which leads to the reduction in the expression of certain genes (e.g., c-myc, p53, thymidine kinase) while inducing the expression of others (e.g., c-fos, aP2); and (3) may involve one or more of the molecular events leading to adipocyte differentiation.
Toscani
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Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
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D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002352:Carrier Proteins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005347:Fibroblasts / Q000187:drug effects / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000187:drug effects*; D006133:Growth Substances / Q000494:pharmacology; D007399:Interphase / Q000187:drug effects; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger / Q000096:biosynthesis; D013937:Thymidine Kinase / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53
D002087:Butyrates; D002352:Carrier Proteins; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D006133:Growth Substances; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D020148:Butyric Acid; D013937:Thymidine Kinase