Estrogen signaling ability in human endometrial cancer through the cancer-stromal interaction

Mitsuyo Matsumoto, Yuri Yamaguchi, Yuko Seino, Atsushi Hatakeyama, Hiroyuki Takei, Hitoshi Niikura, Kiyoshi Ito, Takashi Suzuki, Hironobu Sasano, Nobuo Yaegashi, Shin Ichi Hayashi

研究成果: Article査読

36 被引用数 (Scopus)

抄録

The estrogen pathway plays an important role in the etiology of human endometrial carcinoma (EC). We examined whether estrogen biosynthesis in the tumor microenvironment promotes endometrial cancer. To examine the contribution of stromal cells to estrogen signaling in EC, we used reporter cells stably transfected with the estrogen response element (ERE) fused to the destabilized green fluorescent protein (GFP) gene. In this system, the endometrial cancer stromal cells from several patients activated the ERE of cancer cells to a variable extent. The GFP expression level increased when testosterone, a substrate for aromatase, was added. The effect was variably inhibited by aromatase inhibitors (AIs), although the response to AIs varied among patients. These results suggest that GFP expression is driven by estrogen synthesized by aromatase in the endometrial cancer stromal cells. In a second experiment, we constructed an adenovirus reporter vector containing the same construct as the reporter cells described above, and visualized endogenous ERE activity in primary culture cancer cells from 15 EC specimens. The GFP expression levels varied among the cases, and in most primary tissues, ERE activities were strongly inhibited by a pure anti-estrogen, fulvestrant. Interestingly, a minority of primary tissues in endometrial cancer showed ERE activity independent of the estrogen-ER pathway. These results suggest that AI may have some therapeutic value in EC; however, the hormonal microenvironment must be assessed prior to initiating therapy.

本文言語English
ページ(範囲)451-463
ページ数13
ジャーナルEndocrine-Related Cancer
15
2
DOI
出版ステータスPublished - 2008 6

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 腫瘍学
  • 内分泌学
  • 癌研究

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