Increased expression of histone deacetylase 2 is found in human gastric cancer

Accumulated evidence has established that aberrant regulation of histone deacetylases (HDACs) is one of the major causes of the development of human malignancies. Among different iso‐enzymes of HDAC and sirtuins grouped as the HDAC super family, little is known as to how histone deacetylase 2 (HDAC2) causes carcinogenesis in solid tumors. Here, in order to investigate the possible role of HDAC2 in gastric carcinogenesis, we analyzed the expression of HDAC2 in 71 gastric adenocarcinomas by immunohistochemistry. Moderate to strong expression of HDAC2 was found in 44 (62%) out of a total of 71 tumors. The majority of positive tumors, which were detected in the nucleus but not in normal gastric epithelium, did not express HDAC2 or showed only weak positive staining. Interestingly, we also noted that HDAC2 expression appeared to be associated with tumor aggressiveness as HDAC2 expression was observed to be statistically significant in advanced gastric cancer (P=0.0023, Chi‐square test) and in positive lymph node metastasis (P=0.0713, Chi‐square test). Taken together, these results suggest that HDAC2 may play an important role in the aggressiveness of gastric cancer.

[1]  C. Fenoglio-Preiser,et al.  beta-Catenin mutation is a frequent cause of Wnt pathway activation in gastric cancer. , 2002, Cancer research.

[2]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[3]  Ping Zhu,et al.  Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis. , 2004, Cancer cell.

[4]  W J Macdonald,et al.  GASTRIC CARCINOMA. , 1912, Canadian Medical Association journal.

[5]  J. Ferlay,et al.  Estimates of the worldwide mortality from 25 cancers in 1990 , 1999, International journal of cancer.

[6]  E. Furtado,et al.  Early gastric cancer: Report of 58 cases , 1998, Gastric Cancer.

[7]  R. Frye,et al.  Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. , 2000, Biochemical and biophysical research communications.

[8]  M. Esteller,et al.  Histone deacetylase inhibitors: Understanding a new wave of anticancer agents , 2004, International journal of cancer.

[9]  Esteban Ballestar,et al.  The impact of chromatin in human cancer: linking DNA methylation to gene silencing. , 2002, Carcinogenesis.

[10]  M. Shin,et al.  Inactivating mutations of the caspase-10 gene in gastric cancer , 2002, Oncogene.

[11]  P. Marks,et al.  Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells. , 2000, Journal of the National Cancer Institute.

[12]  K. Kinzler,et al.  Life (and death) in a malignant tumour , 1996, Nature.

[13]  H. Höfler,et al.  Gastric adenocarcinoma: pathomorphology and molecular pathology , 2001, Journal of Cancer Research and Clinical Oncology.

[14]  L. Ngo,et al.  Histone deacetylase (HDAC) inhibitor activation of p21WAF1 involves changes in promoter-associated proteins, including HDAC1. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[15]  H. S. Kim,et al.  Somatic mutations of the trefoil factor family 1 gene in gastric cancer. , 2000, Gastroenterology.

[16]  B. Vogelstein,et al.  A genetic model for colorectal tumorigenesis , 1990, Cell.

[17]  L. Guarente,et al.  Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase , 2000, Nature.

[18]  J. Ferlay,et al.  Erratum: Estimates of the worldwide mortality from 25 cancers in 1990. Int. J. Cancer, 83, 18–29 (1999). , 1999, International journal of cancer.

[19]  U. Weidle,et al.  Inhibition of histone deacetylases: a new strategy to target epigenetic modifications for anticancer treatment. , 2000, Anticancer research.

[20]  Ya-Li Yao,et al.  Isolation and Characterization of cDNAs Corresponding to an Additional Member of the Human Histone Deacetylase Gene Family* , 1997, The Journal of Biological Chemistry.