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*

*この研究の対応する著者

研究成果: Article査読

56 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)539-545
ページ数7
ジャーナルMolecular Human Reproduction
14
9
DOI
出版ステータスPublished - 2008
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 胎生学
  • 細胞生物学
  • 遺伝学
  • 発生生物学
  • 生殖医学
  • 産婦人科学

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