Effects of selenite on estrogen receptor-alpha expression and activity in MCF-7 breast cancer cells

J Cell Biochem. 2000 Aug 2;79(2):282-92. doi: 10.1002/1097-4644(20001101)79:2<282::aid-jcb110>3.0.co;2-v.


To determine whether selenite has estrogen-like activities, the effects of this compound on estrogen receptor-alpha (ER-alpha) and other estrogen-regulated genes were measured in the human breast cancer cell line MCF-7. Treatment of cells with 1 uM of sodium selenite resulted in a 40% decrease in the amount of estrogen receptor-alpha and in a parallel decrease of 40% in ER-alpha mRNA. Progesterone receptor concentration increased 2.6-fold and pS2 mRNA increased 2.4-fold after selenite treatment. The induction of progesterone receptor and pS2 was blocked by the anti-estrogen ICI-182,780. In transient co-transfection experiments of Wild-type ER-alpha and an estrogen response element-reporter construct, selenite stimulated CAT activity. In binding assays, selenite blocked the binding of estradiol to ER-alpha (K(i) = 23 +/- 17 nM, n = 3) suggesting that this compound interacts with the hormone binding domain of the receptor. To determine whether interaction of selenite with the hormone binding domain results in receptor activation, COS-1 cells were transiently co-transfected with the chimeric receptors GAL-ER, which contains the hormone binding domain of ER-alpha and the DNA binding domain of the transcription factor GAL4, and a GAL4-responsive CAT reporter gene. Treatment of cells with estradiol or selenite resulted in a three- to five-fold increase in CAT activity. The effects of selenite on the chimeric receptor were blocked by the antiestrogen, suggesting that selenite activates ER-alpha through an interaction with the hormone binding domain of the receptor. Transfection assays with ER-alpha mutants identified C381, C447, H524, and N532 as interaction sites of selenite with the hormone binding domain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • COS Cells
  • Estradiol / metabolism
  • Estrogen Receptor alpha
  • Humans
  • Protein Binding
  • Proteins / genetics
  • Proteins / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism
  • Sodium Selenite / pharmacology*
  • Trefoil Factor-1
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins


  • Estrogen Receptor alpha
  • Proteins
  • RNA, Messenger
  • Receptors, Estrogen
  • Receptors, Progesterone
  • TFF1 protein, human
  • Trefoil Factor-1
  • Tumor Suppressor Proteins
  • Estradiol
  • Sodium Selenite