Oestrogen receptor-α contributes to the regulation of the hedgehog signalling pathway in ERα-positive gastric cancer

C. Kameda, M. Nakamura, H. Tanaka, A. Yamasaki, M. Kubo, M. Tanaka, H. Onishi, M. Katano

研究成果: ジャーナルへの寄稿学術誌査読

51 被引用数 (Scopus)

抄録

Background: Oestrogen receptor-alpha (ERα) is highly expressed in diffuse-type gastric cancer and oestrogen increases the proliferation of ERα-positive gastric cancer. However, a detailed mechanism by which oestrogen increases the proliferation of these cells is still unclear. Methods:We used 17-Β-oestradiol (E2) as a stimulator against the ERα pathway. Pure anti-oestrogen drug ICI 182 780 (ICI) and small interfering RNA against ERα (ERα siRNA) were used as inhibitors. Cyclopamine (Cyc) was used as the hedgehog (Hh) pathway inhibitor. Two human ERα-positive gastric cancer cells were used as target cells. Effects of the stimulator and inhibitor on E2-induced cell proliferation were also examined.results: In ERα-positive cells, E2 increased not only cell proliferation but also one of the ligands of the Hh pathway, Shh expression. 17-Β-Oestradiol-induced cell proliferation was suppressed by ICI, ERα siRNA or Cyc. The increased expression of Shh induced by E2 was suppressed by ICI and ERα siRNA but not by Cyc. Furthermore, recombinant Shh activated the Hh pathway and increased cell proliferation, whereas anti-Shh antibody suppressed E2-induced cell proliferation. When a relationship between ERα and Shh expressions was analysed using surgically resected gastric cancer specimens, a positive correlation was found, suggesting a linkage between the ERα and Hh pathways.Conclusion:Our data indicate that activation of the ERα pathway promotes cell proliferation by activating the Hh pathway in a ligand-dependent manner through Shh induction of ERα-positive gastric cancer.

本文言語英語
ページ(範囲)738-747
ページ数10
ジャーナルBritish journal of cancer
102
4
DOI
出版ステータス出版済み - 2月 2010

!!!All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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