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Horm Metab Res 2004; 36(7): 437-444
DOI: 10.1055/s-2004-825724
Original Basic
© Georg Thieme Verlag Stuttgart · New York

Impairment of the Antiproliferative Effect of Glucocorticosteroids by 11β-hydroxysteroid Dehydrogenase Type 2 Overexpression in MCF-7 Breast-cancer Cells

C.  Lipka 1 , J.  Mankertz 2 , M.  Fromm 3 , H.  Lübbert 2 , H.  Bühler 4 , W.  Kühn 1 , V.  Ragosch 1 , S.  Hundertmark 1
  • 1Department of Obstetrics and Gynecology, Charité, Germany
  • 2Department of Gastroenterology, Infectiology, and Rheumatology, Charité, Germany
  • 3Department of Clinical Physiology, Charité, Germany
  • 4Department of Obstetrics and Gynecology, Marienhospital Herne, Ruhr-Universität Bochum
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Publikationsverlauf

Received 21 October 2003

Acceped after Revision 26 January 2004

Publikationsdatum:
11. August 2004 (online)

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Abstract

To verify the relevance of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity in controlling breast-cancer cell growth, we have evaluated the correlation of 11β-HSD2 expression and antiproliferative effects of glucocorticosteroids (GCs) on breast cancer cell proliferation. We cloned human 11β-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 11β-HSD activity. Low (times 7) and high (times 718) 11β-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 11β-HSD2; about 50 % of the increase in cell proliferation was attained by low 11β-HSD2 overexpression, while high enzyme overexpression led to an increase in cell growth of about 120 %. Using direct evidence, this study shows 11β-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 11β-HSD inhibitors in the treatment of breast cancer.

Key words

Breast cancer - Glucocorticosteroids

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PD Dr. S. Hundertmark,
Dr. C. Lipka

Frauenklinik · Allgemeines Krankenhaus Altona ·

Paul-Ehrlich-Str. 1 · 22763 Hamburg · Germany

Telefon: + 49/40/88221711

Fax: + 49/40/88224912 ·

eMail: sven.hundertmark@ak-altona.lbk-hh.de

eMail: corinna.lipka@t-online.de