Estrogen receptor-mediated effects of tamoxifen on human endometrial cancer cells

Takako Sakamoto, Hidetaka Eguchi, Yoko Omoto, Takuya Ayabe, Hiroyuki Mori, Shin ichi Hayashi

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)


Tamoxifen is an estrogen receptor (ER)-antagonist that is widely used for the treatment of breast cancer, although it increases the risk of endometrial cancer. The mechanism mediating the stimulatory effect of tamoxifen on endometrial cancer is presently unknown. In this study we examined the effects of tamoxifen on Ishikawa 3H-12 endometrial cancer cells and MCF-7 breast cancer cells. Ishikawa cell growth was stimulated by 4-hydroxytamoxifen and accompanied by increased transcriptional activity of the endogenous ER. These stimulatory effects did not occur in MCF-7 cells. The relative transcriptional activity of the activation function (AF) 1 domain of ERα compared with that of the AF2 domain was 4-fold higher in Ishikawa cells than in MCF-7 cells. Mitogen-activated protein (MAP) kinase, which stimulates the transcriptional activity of AF1, was constitutively activated in Ishikawa cells, but not in MCF-7 cells. These observations suggest that the constitutively activated MAP kinase-signaling pathway in Ishikawa cells enhances the transcriptional activity of ERα via the AF1 domain. This ERα activation pathway may be involved in the stimulatory effect of tamoxifen on the development and/or progression of endometrial cancer.

Original languageEnglish
Pages (from-to)93-104
Number of pages12
JournalMolecular and Cellular Endocrinology
Issue number1-2
Publication statusPublished - 2002 Jun 28
Externally publishedYes


  • Endometrial cancer
  • Estrogen receptor α
  • Tamoxifen

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology


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