Impairment of the antiproliferative effect of glucocorticosteroids by 11beta-hydroxysteroid dehydrogenase type 2 overexpression in MCF-7 breast-cancer cells

Horm Metab Res. 2004 Jul;36(7):437-44. doi: 10.1055/s-2004-825724.


To verify the relevance of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity in controlling breast-cancer cell growth, we have evaluated the correlation of 11beta-HSD2 expression and antiproliferative effects of glucocorticosteroids (GCs) on breast cancer cell proliferation. We cloned human 11beta-HSD2 cDNA into the expression vector pBK-CMV. The interspersing lac promoter region was deleted, achieving differential translational efficiency. The constructs were stably transfected into wild-type MCF-7 breast-cancer cells possessing almost no oxidative and no reductive 11beta-HSD activity. Low (times 7) and high (times 718) 11beta-HSD2 overexpression was achieved. We compared growth behavior of transfected cells In the presence of GCs to MCF-7 cells transfected with pBK-CMV alone (internal control). The antiproliferative effects of GCs were reversed and total cell growth boosted by overexpression of 11beta-HSD2; about 50 % of the increase in cell proliferation was attained by low 11beta-HSD2 overexpression, while high enzyme overexpression led to an increase in cell growth of about 120 %. Using direct evidence, this study shows 11beta-HSD2 to impair antiproliferative glucocorticosteroid effects, thus acting as an enzymatic shield aggravating breast-cancer cell growth. These results indicate a possible therapeutic role for 11beta-HSD inhibitors in the treatment of breast cancer.

Publication types

  • Comparative Study

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 2 / genetics
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2 / metabolism*
  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology*
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Cell Division / drug effects
  • Cloning, Molecular
  • Gene Expression Regulation, Neoplastic / physiology
  • Glucocorticoids / pharmacology*
  • Humans
  • Receptors, Glucocorticoid / metabolism
  • Receptors, Mineralocorticoid / metabolism
  • Transfection
  • Tumor Cells, Cultured


  • Glucocorticoids
  • Receptors, Glucocorticoid
  • Receptors, Mineralocorticoid
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2