The proportion of gastric cancers positive for estrogen receptor (ER)-α expression is reported to be between 0-67%, depending upon the study. The role of ER-α in gastric carcinogenesis is unclear. The ER-α gene is located at chromosome 6q25.1, and the long arm of chromosome 6 has been known as a site with frequent loss of heterozygosity (LOH) in gastric cancer. ER expression is linked to suppression of cell proliferation in vitro. Epigenetic inactivation might explain the loss of ER-α gene expression in gastric cancer. Given there is no information available regarding the methylation status of the ER-α gene promoter region in gastric cancer, we investigated such methylation in 13 gastric cancer cell lines. Western blot analysis, reverse transcription-polymerase chain reaction (PCR), methylation-specific PCR (MS-PCR) and bisulfite sequencing analyses were used. ER-α protein was not detected in any cell line, although ER-α mRNA was detected in 1 of 13 gastric cancer cell lines. MS-PCR and bisulfite sequencing showed all 13 gastric cancer cell lines had methylated CpG regions in their ER-α gene promoters. In conclusion, inactivation of ER-α gene expression in gastric cancer cell lines appears associated with CpG island methylation near the TGA initiation codon of the ER-α gene.

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