Hypomethylation of the metastasis-associated S100A4 gene correlates with gene activation in human colon adenocarcinoma cell lines.
The DNA methylation status of the metastasis-associated S100A4 gene in S100A4-positive and -negative human colon adenocarcinoma cell lines was examined. Northern and Western blot analyses revealed that HT-29, SW480, SW620, WiDr and Colo201 cells expressed S100A4, whereas SW837, LoVo and DLD-1 cells expressed little S100A4. Using CpG methylation-sensitive and -insensitive restriction enzymes and PCR-based methylation assay, it was found that the S100A4 gene in HT-29, SW480, SW620, WiDr and Colo201 cells, but not in SW837, LoVo and DLD-1 cells, was hypomethylated and that the hypomethylation of the second intron was correlated well with the expression of S100A4. 5-Aza-2'-deoxycytidine, an inhibitor of the eukaryotic DNA methyltransferase, induced the expression of the S100A4 gene in SW837, LoVo and DLD-1 cells, while it showed no effect on the expression of the gene in WiDr cells. These results indicate that hypomethylation of the S100A4 gene results in the expression of the gene in colon adenocarcinoma cells.
Nakamura
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N
Division of Chemotherapy, Chiba Cancer Center Research Institute, Japan.
Takenaga
K
K
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D005786:Gene Expression Regulation / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000096:biosynthesis / Q000235:genetics*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human; D000077209:Decitabine; D001374:Azacitidine