Histone H4 acetylation and histone deacetylase 1 expression in esophageal squamous cell carcinoma.
The alterations of the chromatin structure by histone acetylases (HATs) and histone deacetylases (HDACs) are implicated in the regulation of gene transcription and also in the process of carcinogenesis. HDAC inhibitors have been shown to be potent inducers of growth arrest, differentiation and/or apoptotic cell death of transformed cells and, as a result, they are currently receiving considerable attention as antitumor agents. In this study, we examined the status of histone H4 acetylation and the level of HDAC1 expression in surgically resected specimens of human esophageal squamous cell carcinoma by immunohistochemistry. We herein demonstrate that histone H4 of esophageal carcinoma cells was significantly hyperacetylated in the early stage of cancer invasion and thereafter changed into a hypoacetylated state according to the degree of cancer progression. The cases in which HDAC1 was less expressed in esophageal carcinoma cells than in the normal mucosa significantly increased as the carcinoma invaded into the deeper layers of the esophageal wall. Furthermore, both the hyperacetylation of histone H4 and the high expression of HDAC1 were shown to topologically colocalize in the same tumor. These results suggested that a dynamic equilibrium between the HAT and HDAC activities is disrupted in esophageal carcinoma, thus implying that a certain interaction may exist between the hyperacetylation of histone H4 and the HDAC1 expression.
Toh
Yasushi
Y
Department of Gastroenterological Surgery, National Kyushu Cancer Center, Fukuoka 811-1395, Japan. ytoh@nk-cc.go.jp
Yamamoto
Manabu
M
Endo
Kazuya
K
Ikeda
Yasuharu
Y
Baba
Hideo
H
Kohnoe
Shunji
S
Yonemasu
Hirotoshi
H
Hachitanda
Yoichi
Y
Okamura
Takeshi
T
Sugimachi
Keizo
K
D000107:Acetylation; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000473:pathology; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D009361:Neoplasm Invasiveness
D006657:Histones; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases