Analysis of the methylation status of genes up-regulated by the demethylating agent, 5-aza-2'-deoxycytidine, in esophageal squamous cell carcinoma

Makoto Arai; Fumio Imazeki; Yuzo Sakai; Rintaro Mikata; Motohisa Tada; Naohiko Seki; Hideaki Shimada; Takenori Ochiai; Osamu Yokosuka

Analysis of the methylation status of genes up-regulated by the demethylating agent, 5-aza-2'-deoxycytidine, in esophageal squamous cell carcinoma

Oncol Rep. 2008 Aug;20(2):405-12.

Authors

Makoto Arai¹, Fumio Imazeki, Yuzo Sakai, Rintaro Mikata, Motohisa Tada, Naohiko Seki, Hideaki Shimada, Takenori Ochiai, Osamu Yokosuka

Affiliation

¹ Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan. araim-cib@umin.ac.jp

PMID: 18636205

Abstract

To determine the clinical significance of gene promoter methylation in esophageal squamous cell carcinoma (ESCC), we examined the promoter methylation status of genes showing elevated expression, as determined by DNA microarray-based transcriptomic analysis, in three ESCC cell lines (TE-1, TE-2, TE-10) after 5-aza-2'-deoxycytidine (DAC) treatment. We observed a high degree of DNA methylation within the promoter regions of three genes, namely cathepsin L2 (CTSL2), normal mucosa of esophagus specific 1 (NMES1), and fatty acid binding protein 5 (FABP5). Overexpression of NMES1 in ESCC cell lines increased cell motility. Down-regulation of NMES1 might play an important role in the cell motility of ESCC or be a potent marker of malignancy.

MeSH terms

Antimetabolites, Antineoplastic / pharmacology*
Azacitidine / analogs & derivatives*
Azacitidine / pharmacology
Carcinoma, Squamous Cell / drug therapy
Carcinoma, Squamous Cell / genetics*
Carcinoma, Squamous Cell / metabolism
Cathepsin L
Cathepsins / genetics
Cathepsins / metabolism
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects
Cysteine Endopeptidases / genetics
Cysteine Endopeptidases / metabolism
DNA Methylation / drug effects*
DNA Modification Methylases / antagonists & inhibitors
Decitabine
Esophageal Neoplasms / drug therapy
Esophageal Neoplasms / genetics*
Esophageal Neoplasms / metabolism
Esophagus / metabolism
Fatty Acid-Binding Proteins / genetics
Fatty Acid-Binding Proteins / metabolism
Gene Expression Regulation, Neoplastic / drug effects*
Humans
Neoplasm Proteins / genetics*
Neoplasm Proteins / metabolism
Nuclear Proteins / genetics*
Nuclear Proteins / metabolism
Promoter Regions, Genetic / genetics
RNA, Messenger / genetics
RNA, Messenger / metabolism
Reverse Transcriptase Polymerase Chain Reaction

Substances

Antimetabolites, Antineoplastic
Cell Cycle Proteins
FABP5 protein, human
Fatty Acid-Binding Proteins
GADD45A protein, human
Neoplasm Proteins
Nuclear Proteins
RNA, Messenger
c15orf48 protein, human
Decitabine
DNA Modification Methylases
Cathepsins
Cysteine Endopeptidases
CTSL protein, human
Cathepsin L
Azacitidine