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Horm Metab Res 2008; 40(11): 772-778
DOI: 10.1055/s-2008-1080897
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Modulation of 11β-Hydroxysteroid Dehydrogenase Expression by Bombesin: A Possible Mechanism for Glucocorticoid Resistance in Androgen Independent Prostate Cancer

J. G. Lee 1 , R. Ge 2 , D. O. Hardy 2 , K. Leong 1 , D. M. Nanus 3 , M. P. Hardy 2 , R. Shen 1
  • 1Department of Urology, Urological Oncology laboratory, Weill Medical College of Cornell University, New York, USA
  • 2Population Council, Weill Medical College of Cornell University, New York, USA
  • 3Department of Medicine, Weill Medical College of Cornell University, New York, USA
Further Information

Publication History

received 21.11.2007

accepted 28.03.2008

Publication Date:
22 August 2008 (online)

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Abstract

Treatment with glucocorticoids is one of a limited number of options for androgen independent prostate cancer. Neuroendocrine differentiation has been shown to contribute to androgen-independent prostate cancer progression. To study the potential link between neuroendocrine differentiation and the glucocorticoid action, we investigated the effects of the product of neuroendocrine differentiation – bombesin on glucocorticoid metabolizing enzymes – 11β-hydroxysteroid dehydrogenases in PC-3 cells. Our Western analysis, RT-PCR, and activity assays demonstrate that while 18-hour exposure to bombesin reduces 11β-hydroxy-steroid dehydrogenases-1 profiles (activities 25% less, protein level 29% lower, mRNA levels 45% lower), contrarily it increases 11β-hydroxysteroid dehydrogenases-2 profiles (activities 34%, protein levels 100%, mRNA levels 120%). Blockade bombesin action with bombesin receptor antagonists and the enzyme degrading bombesin prevented these changes, suggesting the observed modulations were bombesin receptor-specific. In addition, bombesin increased the amounts of interleukin-8 and mRNA of vascular endothelial growth factor receptor 2, which were lowered in the presence of cortisol, suggesting that neuropeptide blockade may extend the benefits of glucocorticoids in treating androgen-independent prostate cancer.

Key words

glucocorticoid - bombesin - 11β-hydroxysteroid dehydrogenases - neuroendocrine differentiation - prostate cancer

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Correspondence

R. Shen

Weill Medical College of Cornell University

Dept of Urology

Rm F-902, Box 94

1300 York Ave

10021 New York

USA

Phone: +1/212/746 50 28

Fax: +1/212/746 89 41

Email: rshen@med.cornell.edu

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