Gene expression profiling induced by histone deacetylase inhibitor, FK228, in human esophageal squamous cancer cells.

Histone deacetylase inhibitors (HDACIs) are promising therapeutic agents with the potential for regulating cell cycle, differentiation and apoptosis in cancer cells. HDACI activity is associated with selective transcriptional regulation and altering gene expression. However, the exact mechanisms leading to the antitumor effect of HDACIs are not fully understood. FK228, one of the powerful HDACIs, strongly inhibited cell growth of T.Tn and TE2 cells and induced apoptosis. Therefore, comprehensive analysis of the changes in gene expression in human esophageal cancer cell lines by the HDACI FK228 was carried out by microarray analysis. This analysis was used to clarify the expression profiles of genes after exposure to FK228. Of the 4,608 genes analyzed, 93 genes in T.Tn and 65 genes in TE2 were up- or down-regulated 2-fold or more at least at one time point during FK228 exposure and they were classified into four clusters based on their expression patterns. Among them, 15 genes were contained in both cell lines and their expression patterns were similar. Except p21, Prdx1 (reported by us) and IGFBP3, the behaviour/expression of 12 highly responsive genes has still not been reported in esophageal cancer cells. These observations of the expression patterns of functionally classified genes provided insights into the mechanism of the antitumor effect of FK228 in esophageal squamous carcinoma.