Downregulation of gelsolin and retinoic acid receptor beta expression in gastric cancer tissues through histone deacetylase 1.
OBJECTIVE
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 HDAC1 overexpression and might play some role in gastric carcinogenesis.
Kim
Jin-Hyun
JH
Department of Veterinary Pathology, Seoul National University, Korea.
Choi
Yang-Kyu
YK
Kwon
Ho-Jeong
HJ
Yang
Han-Kwang
HK
Choi
Jae-Hoon
JH
Kim
Dae-Yong
DY
D015536:Down-Regulation; D018260:Gelsolin / Q000378:metabolism*; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism*
D018260:Gelsolin; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases