Analysis of the methylation status of genes up-regulated by the demethylating agent, 5-aza-2'-deoxycytidine, in esophageal squamous cell carcinoma.
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.
Arai
Makoto
M
Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan. araim-cib@umin.ac.jp
Imazeki
Fumio
F
Sakai
Yuzo
Y
Mikata
Rintaro
R
Tada
Motohisa
M
Seki
Naohiko
N
Shimada
Hideaki
H
Ochiai
Takenori
T
Yokosuka
Osamu
O
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D056668:Cathepsin L; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D004947:Esophagus / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000097642:GADD45 Proteins
D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine; D056668:Cathepsin L; D002403:Cathepsins; D018797:Cell Cycle Proteins; D003546:Cysteine Endopeptidases; D015254:DNA Modification Methylases; D000077209:Decitabine; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C493412:FABP5 protein, human; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C465665:C15orf48 protein, human; C534281:CTSL protein, human