Estrogenic and antiestrogenic activities of 16alpha- and 2-hydroxy metabolites of 17beta-estradiol in MCF-7 and T47D human breast cancer cells

J Steroid Biochem Mol Biol. 1998 Dec;67(5-6):413-9. doi: 10.1016/s0960-0760(98)00135-6.


The comparative mitogenic activities of 17beta-estradiol (E2) and four metabolites, 2-hydroxyestradiol (2-OHE2), 2-hydroxyestrone (2-OHE1), 16alpha-hydroxyestradiol (16alpha-OHE2) and 16alpha-hydroxyestrone (16alpha-OHE1) were determined in estrogen receptor (ER)-positive MCF-7 and T47D human breast cancer cells. E2 (1 nM) induced a 7- to 13-fold increase in cell number in both cell lines compared to untreated cells and the mitogenic potencies of 16alpha-OHE1 or 16alpha-OHE2 were comparable to or greater than E2. In contrast, 2-OHE1 and 2-OHE2 were weak mitogens in both cell lines and in cells cotreated with 1 nM E2 and 100 or 1000 nM 2-OHE1 or 2-OHE2, there was a significant inhibition of hormone-induced cell proliferation. The comparative ER agonist/antagonist activities of E2 and the metabolites on transactivation were determined in T47D cells transiently transfected with constructs containing promoter inserts from the cathepsin D (pCD) and creatine kinase B (pCKB) genes. E2, 16alpha-OHE2 and 16alpha-OHE1 induced reporter gene activity in both MCF-7 or T47D cells transfected with pCKB or pCD. In contrast, 2-OHE1 and 2-OHE2 did not exhibit ER agonist activity for these transactivation assays, but in cells cotreated with E2 plus 2-OHE1 or 2-OHE2, there was a significant decrease in the hormone-induced response. These results demonstrate that 16alpha-OHE1/16alpha-OHE2 exhibit estrogenic activities similar to that observed for E2, whereas the 2-catecholestrogens are weak ER agonists (cell proliferation) or antagonists (cell proliferation and transactivation).

Publication types

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

MeSH terms

  • Breast Neoplasms
  • Cathepsin D / biosynthesis
  • Cathepsin D / genetics
  • Cell Division / drug effects*
  • Creatine Kinase / biosynthesis
  • Creatine Kinase / genetics
  • Estradiol / analogs & derivatives*
  • Estradiol / pharmacology*
  • Estriol / pharmacology
  • Female
  • Humans
  • Hydroxyestrones / pharmacology
  • Isoenzymes
  • Promoter Regions, Genetic
  • Receptors, Estrogen / physiology
  • Recombinant Proteins / biosynthesis
  • Transfection
  • Tumor Cells, Cultured


  • Hydroxyestrones
  • Isoenzymes
  • Receptors, Estrogen
  • Recombinant Proteins
  • 16-hydroxyestrone
  • Estradiol
  • 2-hydroxyestradiol
  • Creatine Kinase
  • Cathepsin D
  • Estriol
  • 2-hydroxyestrone