Expression of the 11β-hydroxysteroid dehydrogenase type II enzyme in breast tumors and modulation of activity and cell grow-th in PMC42 cells

Manipulating the metabolism of glucocorticoids may serve as a useful adjunct in the treatment of breast cancer. The 11 beta -hydroxysteroid dehydrogenase type 2 enzyme (11 beta HSD2) potently inactivates glucocorticoids thereby protecting the non-selective mineralocorticoid receptor (MR) in fluid transporting tissues. In the present study, Western blot analysis showed the presence of 11 beta HSD2 in 66% of the breast tumor samples. The 11 beta HSD2 and MR are also present in the breast tumor cell line PMC42. Glycyrrhetinic acid abolished glucocorticoid metabolism and inhibited cell growth by 40%, the latter at concentrations consistent with glucocorticoid receptor (GR) and MR binding studies. Metabolism was increased by glucocorticoids, the anti-glucocorticoid RU 38486 and anti-mineralocorticoid spironolactone, while aldosterone had no effect. Neither cortisol nor aldosterone affected cell proliferation, but both RU 38486 and spironolactone caused a significant decrease in cell number. The effects of RU 38486 were only observed at micromolar concentrations and are inconsistent with an action via GR or progesterone receptor (PR). This study shows that 11 beta HSD2 activity and cell proliferation of PMC42 cells can be modulated via steroid receptors. (C) 2001 Elsevier Science Ltd. All rights reserved.