Expression and Regulation of 11-β Hydroxysteroid Dehydrogenase Type 2 Enzyme Activity in the Glucocorticoid-Sensitive CEM-C7 Human Leukemic Cell Line. (17th March 2013)

• Record Type: Journal Article
• Authors: Garbrecht, Mark R.; Schmidt, Thomas J.
• Other Names: Balaram P. Academic Editor.; Guo Z. S. Academic Editor.; Khong H. T. Academic Editor.; Mo H. Academic Editor.
• Is Part Of: ISRN oncology. Volume 2013(2013)
• Publication Date: 2013-03-17
• Subjects: Oncology -- Periodicals; Neoplasms; Oncology; Periodicals; 616.994
• DOI: 10.1155/2013/245246
• Languages: English
• ISSNs: 2090-5661

Abstract

Abstract : Glucocorticoids are commonly used in the first-line treatment of hematological malignancies, such as acute lymphoblastic leukemia, due to the ability of these steroids to activate pro-apoptotic pathways in human lymphocytes. The goal of the current study was to examine the gene expression and enzyme activity of the microsomal enzyme, 11- β hydroxysteroid dehydrogenase type 2 (HSD11B2, HSD2), which is responsible for the oxidation of bioactive glucocorticoids to their inert metabolites. Using the glucocorticoid-sensitive human leukemic cell line, CEM-C7, we were able to detect the expression of HSD2 at the level of mRNA (via RT-PCR), protein (via immunohistochemistry and immunoblotting), and enzyme activity (via conversion of tritiated cortisol to cortisone). Furthermore, we observed that HSD2 enzyme activity is down regulated in CEM-C7 cells that were pretreated with the synthetic glucocorticoid, dexamethasone (100 nM, <15 hours), and that this down regulation of enzyme activity is blocked by the administration of the glucocorticoid receptor antagonist, RU-486. Taken collectively, these data raise the possibility that the effectiveness of glucocorticoids in the treatment of human leukemias may be influenced by: (1) the ability of these neoplastic cells to metabolize glucocorticoids via HSD2 and (2) the ability of these steroids to regulate the expression of this key enzyme.