Brief Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jan 28, 2011; 17(4): 526-533
Published online Jan 28, 2011. doi: 10.3748/wjg.v17.i4.526
Silence of HIN-1 expression through methylation of its gene promoter in gastric cancer
Yan Gong, Ming-Zhou Guo, Zhi-Jia Ye, Xiu-Li Zhang, Yong-Liang Zhao, Yun-Sheng Yang
Yan Gong, Ming-Zhou Guo, Xiu-Li Zhang, Yun-Sheng Yang, Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing 100853, China
Zhi-Jia Ye, Department of Genetics, Yale Medical School TAC, S320 1 Gilbert Street, New Haven, CT 06520, United States
Yong-Liang Zhao, Department of General Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
Author contributions: Gong Y and Yang YS performed the majority of experiments; Guo MZ and Ye ZJ provided vital reagents and analytical tools and edited the manuscript; Zhao YL and Zhang XL collected all the specimens for this work; Gong Y and Guo MZ designed the study and wrote the manuscript.
Supported by National Basic Research Program (973 Program No. 2010CB912802) and the Postdoctoral Fund of China, No. 20080441314
Correspondence to: Yun-Sheng Yang, MD, PhD, Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, China. sunny888@medmail.com.cn
Telephone: +86-10-68182255 Fax: +86-10-68212267
Received: September 2, 2010
Revised: November 2, 2010
Accepted: November 9, 2010
Published online: January 28, 2011
Abstract

AIM: To clarify the role of high in normal-1 (HIN-1) gene promoter methylation during gastric cancer development.

METHODS: Gastric cancer cell lines and tissue specimens were analyzed for expression of HIN-1 mRNA and protein using the semi-quantitative reverse transcription polymerase chain reaction and immunohistochemistry. The methylation of the HIN-1 gene promoter was detected in gastric carcinoma cells and tissues using methylation-specific polymerase chain reaction. The 3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium cell viability assay and flow cytometry were used to assess the changes in behaviors of gastric cancer cells with or without 5-aza-2’-deoxycytidine treatment.

RESULTS: HIN-1 was not expressed in 4 of 5 gastric cancer cell lines. The demethylation reagent 5-aza-2’-deoxycytidine was able to induce or upregulate HIN-1 expression in gastric cancer cell lines, which is associated with reduction of tumor cell viability. Furthermore, methylation of the HIN-1 gene promoter was shown in 57.8% (26/45) of the primary gastric cancer and 42.1% (17/38) of adjacent tissue samples, but was not shown in normal gastric mucosa (0/10). From the clinicopathological data of the patients, methylation of the HIN-1 gene promoter was found to be associated with tumor differentiation (P = 0.000).

CONCLUSION: High methylation of HIN-1 gene promoter results in silence of HIN-1 expression in gastric cancer. 5-aza-2’-deoxycytidine reverses HIN-1 methylation and reduces viability of gastric cancer cells.

Keywords: High in normal-1; Gene methylation; 5-aza-2’-deoxycytidine; Tumor differentiation; Gastric cancer