Down-regulation of estrogen receptor by the methylation of the estrogen receptor gene in endometrial carcinoma

Anticancer Res. 2002 Jan-Feb;22(1A):139-43.

Abstract

Background: Human uterine endometrial carcinomas are composed of estrogen receptor (ER)-positve and ER-negative subgroups, though the mechanisms that down-regulate the ER expression are not understood. The present study was undertaken to examine the involvement of methylation of the ER gene on the ER status.

Materials and methods: DNA was extracted from 25 cases of endometrial carcinoma. Polymerase chain reaction (PCR), using the extracted DNA and methylation-sensitive restriction enzymes (Hpa II, Hha I), was performed to detect the methylation of a CpG island in the ER (alpha) gene. The results were compared with the ER expression by immunostaining.

Results: In the 25 endometrial carcinomas, methylation at the Hpa II site, or at both the Hpa II and Hha I sites, was found in 6 cases, while methylation was not found in the remaining 19 cases. Immunohistochemically, 5 of the 6 methylation-positive cases were negative for ER, whereas 14 of the 19 methylation-negative cases were ER-positive (p=0.02).

Conclusion: Methylation of the CpG island of the ER gene is inversely correlated with ER expression in a subset of endometrial carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • CpG Islands / genetics
  • DNA Methylation*
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / metabolism
  • Down-Regulation
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology
  • Estrogen Receptor alpha
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Neoplasm Staging
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Estrogen / biosynthesis
  • Receptors, Estrogen / genetics*
  • Tumor Cells, Cultured

Substances

  • DNA, Neoplasm
  • Estrogen Receptor alpha
  • RNA, Messenger
  • Receptors, Estrogen