Estrogen and aryl hydrocarbon responsiveness of ECC-1 endometrial cancer cells

Emely Castro-Rivera, Mark Wormke, Stephen Safe

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


ECC-1 endometrial cancer cells express estrogen receptor α (ER(α), and 17β-estradiol (E2) induces cell proliferation, cathepsin D mRNA levels, and reporter gene activity in cells transiently transfected with constructs derived from the human cathepsin D and creatine kinase B (pCD and pCKB, respectively) gene promoters. The comparative antiestrogenic activity of aryl hydrocarbon receptor (AhR) agonists and ER(α) antagonists were also determined in these endometrial cancer cells. A functional AhR was expressed in ECC-1 cells and AhR agonists including 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD) inhibited E2-induced cell proliferation and transactivation. This was comparable to inhibitory AhR-ER crosstalk in breast cancer cell lines. The pure ER antagonist 1CI 182,780 also exhibited antiestrogenic activity in ECC-1 cells: however, the results obtained for 4'- hydroxytamoxifen were response-specific. 4'-Hydroxytamoxifen alone did not induce ECC-1 cell proliferation but completely inhibited E2-induced cell proliferation. 4'-Hydroxytamoxifen primarily exhibited ER antagonist activities in transactivation assays and this contrasted to the predominant ER agonist responses observed in other endometrial cancer cell lines. The unique cellular context of ECC-1 cells was confirmed using pCKB and constructs expressing wild-type ER or ER variants expressing activation function 1 (AF1) or AF2 (ER-AF1 and ER-AF2, respectively). 4'- Hydroxytamoxifen did not induce reporter gene activity in cells cotransfected with pCKB and ER-AF1 or ER-AF2; however, in cotreatment studies (4'- hydroxytamoxifen plus E2), 4'-hydroxytamoxifen inhibited E2-induced transcriptional activation by ER-AF1 or ER-AF2. Thus, the primarily antiestrogenic activity observed for 4'-hydroxytamoxifen in ECC-1 cells may be related to the inability to activate gene expression through AF1-dependent pathways.

Original languageEnglish (US)
Pages (from-to)11-21
Number of pages11
JournalMolecular and cellular endocrinology
Issue number1-2
StatePublished - Apr 25 1999


  • Ah receptor
  • Antiestrogen
  • ECC-1
  • Endometrial cells
  • Estrogen

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology


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