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KMID : 0882420040660050504
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Korean Journal of Medicine
2004 Volume.66 No. 5 p.504 ~ p.512
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Loss of estrogen receptor-alpha, ER-a and promoter hypermethylation in gastric cancer
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Woo In-Sook
Moon Do-Ho
Kim Seong-Hun
Im So-Hee
Lee Myung-Ah
Kang Jin-Hyoung
Hong Young-Seon
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Abstract
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Background: The significance of ER expression and hormone manipulation in gastric cancer is not established. There have been several reports supporting the role of the TR gene as tumor suppressor gene in carcinogenesis. The ER- a gene is located on chromosome (;(125.1. Deletions of the long arm of chromosome 6 are cor7umon in gastric carcinoma, suggesting the presence of tumor suppressor genes in this region. The proportion of ER-positive gastric cancers ranges between 0`.%ti and 67% depending on the method of detection. Epigenetic inactivation might explain the loss of ER- a gene expression in gastric cancer. There is no information available regarding the methylation status of the ER a gene promoter region in gastric cancer so far-. The aim of this study was to assess the expression of ER- a in gastric cancer cell lines and determine whether methylation of the 5´ promoter region is associated with loss of ER- a expression in gastric cancer.
Methods: We investigated such methylation in 13 gastric cancer cell lines. Western blot analysis, reverse transcription-polymerase chain reaction (PCR), methylation-specific PCR (NIS-PCR) and bisulfite sequencing analyses were used. Irnmunohistochemical staining for the ER- a gene was dome for forty-two paraffin embedded tissues from gastric cancer patients.
Results: ER- a protein was not detected in any cell line, 171?- a mRNA was expressed in only Kato III cell line. NIS-PCR and bisulfite sequencing showed all thirteen gastric cancer cell lines had methylated CpG regions in their ER- a gene promoters. Immunohistochemical staining of ER a showed no positivity in any of examined srmlples.
Conslusion:Inactivation of ER- a gene expression in gastric cancer cell lines appears associated with CpG island methylation near the TGA initiation codon of the EIZ- a gene.(Korean j Med 66:504-512, 2004)
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KEYWORD
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Estrogen receptor, Methylation, Gastric cancer
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