Potential link between estrogen receptor-α gene hypomethylation and uterine fibroid formation

Hiromi Asada, Yoshiaki Yamagata, Toshiaki Taketani, Aki Matsuoka, Hiroshi Tamura, Naoko Hattori, Jun Ohgane, Naka Hattori, Kunio Shiota, Norihiro Sugino

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Uterine leiomyomas are the most common uterine tumors in women. Estrogen receptor-α (ER-α) is more highly expressed in uterine leiomyomas than in normal myometrium, suggesting a link between uterine leiomyomas and ER-α expression. DNA methylation is an epigenetic mechanism of gene regulation and plays important roles in normal embryonic development and in disease progression including cancers. Here, we investigated the DNA methylation status of the ER-α promoter region (-1188 to +229 bp) in myometrium and leiomyoma. By sodium bisulfite sequencing, 49 CpG sites in the proximal promoter region of ER-α gene were shown to be unmethylated in both leiomyoma and normal myometrium. At seven CpG sites in the distal promoter region of the ER-α gene, there was a variation in DNA methylation status in myometrium and leiomyoma. Further analysis of the DNA methylation status by bisulfite restriction mapping among 11 paired samples of myometrium and leiomyoma indicated that CpG sites in the distal region of ER-α promoter are hypomethylated in leiomyomas of nine patients. In those patients, ER-α mRNA levels tended to be higher in the leiomyoma than in the myometrium. In conclusion, there was an aberrant DNA methylation status in the promoter region of ER-α gene in uterine leiomyoma, which may be associated with high ER-α mRNA expression.

Original languageEnglish
Pages (from-to)539-545
Number of pages7
JournalMolecular Human Reproduction
Volume14
Issue number9
DOIs
Publication statusPublished - 2008
Externally publishedYes

Keywords

  • DNA methylation
  • Epigenetics
  • ER-α promoter
  • Estrogen receptor-α
  • Leiomyoma

ASJC Scopus subject areas

  • Molecular Biology
  • Embryology
  • Cell Biology
  • Genetics
  • Developmental Biology
  • Reproductive Medicine
  • Obstetrics and Gynaecology

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  • Cite this

    Asada, H., Yamagata, Y., Taketani, T., Matsuoka, A., Tamura, H., Hattori, N., Ohgane, J., Hattori, N., Shiota, K., & Sugino, N. (2008). Potential link between estrogen receptor-α gene hypomethylation and uterine fibroid formation. Molecular Human Reproduction, 14(9), 539-545. https://doi.org/10.1093/molehr/gan045