Direct Inhibition of the Expression of Cyclin D1 Gene by Sodium Butyrate

In the mouse fibroblasts BP-A31 as well as in the human epidermoid carcinoma cells KB-3-1, both cyclin D1 mRNA and protein contents decreased rapidly during incubation with sodium butyrate. The decrease of cyclin D1 mRNA was not prevented by cycloheximide indicating that protein synthesis is not required for the inhibition of the expression of cyclin D1 gene by sodium butyrate. The 973 bp region upstream of the human cyclin D1 gene conferred inhibition of the expression of an indicator gene in transiently transfected cells. An 11 base-pair segment situated within this region, with a strong homology to the butyrate-response consensus element identified in butyrate-inducible promoters, also caused an inhibition of transcription under these conditions, indicating that cyclin D1 expression is inhibited by butyrate at the transcriptional level.