Downregulation of gelsolin and retinoic acid receptor β expression in gastric cancer tissues through histone deacetylase 1

Background and Aim: Overexpression of histone deacetylase (HDAC)1, which controls the expression of genes related to cell cycle and apoptosis, has recently been reported in gastric cancer (GC) tissues. In the present study, the pattern of gelsolin and retinoic acid receptor (RAR)beta expression in GC tissues showing HDAC1 overexpression was investigated. Methods: Expression profiles of HDAC1, gelsolin, and RARbeta were evaluated and compared using reverse transcription-polymerase chain reaction, immunoblotting, and immunohistochemical analyses with 22 paired primary human GC tissues and corresponding normal tissues. Results: Compared-with normal gastric tissue, increased expression of HDAC1 mRNA and protein was detected in 17 (77.3%) of 22 GC tissues, while decreased expressions of gelsolin mRNA and protein were shown in 15 (68.1%) samples. Concomitantly, expressions of RARbeta mRNA and protein were decreased in 16 (72.7%) and 17 (77.3%), respectively. Among 17 GC tissues with increased HDAC1 expression, the expressions of gelsolin and RARbeta were simultaneously decreased in 14 (82.4%) and 15 (88.2%) GC tissues, which indicates a strong inverse correlation between HDAC1 and gelsolin/ RARbeta expressions. Correlation between HDAC1 and gelsolin/RARbeta was also confirmed by immunohistochemistry. Conclusions: Taken together, the results of the present study reveal that silencing of gelsolin and RARbeta occurs in GC tissues probably through HDAC I overexpression and might play some role in gastric carcinogenesis. (C) 2004 Blackwell Publishing Asia Pty Ltd.