Effects of cell density and trichostatin A on the expression of HDAC1 and p57Kip2 in Hep 3B cells.
The interplay between the acetylation and deacetylation activities within the cell has been postulated to be a mechanism by which the cell regulates expression from genes at the level of chromatin. We have examined the expression pattern of the human histone deacetylase gene HDAC1 and the cyclin dependent kinase inhibitor p57Kip2 in the hepatocellular carcinoma cell line Hep 3B. HDAC1 expression was elevated at low cell densities, but once a critical threshold point in cell density was attained, expression was reduced to very low levels. Treatment of the cells with trichostatin A (TSA), a potent inhibitor of histone deacetylases, was found to affect expression. p57Kip2 was found to be downregulated by TSA, whereas HDAC1 was upregulated. These effects were found to be cell density dependent. The results suggest that HDAC1 plays a role in its own regulation, and that investigations using TSA should be carried out when cells grow exponentially.
Gray
S G
SG
Laboratory for Molecular Development and Tumour Biology, Karolinska Institute, Stockholm, Sweden.
Ekström
T J
TJ
D002452:Cell Count; D002455:Cell Division / Q000235:genetics; D050761:Cyclin-Dependent Kinase Inhibitor p57; D015536:Down-Regulation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D056284:Histone Deacetylase 1; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007231:Infant, Newborn; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D009687:Nuclear Proteins; D012333:RNA, Messenger; C012589:trichostatin A; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases