| Autor: |
Wim J. E. Tissing, M. Lauten, Carmela Beger, Ivonne Fernandez-Munoz, Katrin Gerdes, Karl Welte, Martin Schrappe |
| Rok vydání: |
2003 |
| Předmět: |
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| Zdroj: |
British Journal of Haematology. 122:245-252 |
| ISSN: |
0007-1048 |
| Popis: |
Glucocorticoids are broadly used for chemotherapy in childhood acute lymphoblastic leukaemia (ALL). The intracellular effects of glucocorticoids are mediated through the glucocorticoid receptor. The human glucocorticoid receptor gamma isoform (hGR-gamma) differs from the main isoform (hGR-alpha) by an additional amino acid within the DNA binding domain of the receptor protein. This may decrease hGR-alpha-mediated transcriptional activation. The importance of hGR-gamma expression in childhood ALL is unknown. To evaluate hGR-gamma mRNA expression levels, a real-time polymerase chain reaction (PCR)-based approach, allowing the selective amplification of hGR-gamma, was developed and optimized. We were able to demonstrate target selectivity of hGR-gamma amplification using sequence-specific primers. Studying the structure of the 3' end of hGR-gamma, a combination of this isoform with other hGR isoforms could be demonstrated. Using analysis of hGR-gamma-specific amplification in comparison with the expression of hGR-total (all isoforms) in leukaemic blasts from patients with either a good response to prednisone (PGR) or poor-prednisone response (PPR) in vivo, relative hGR-gamma expression was observed to be lower in cells from patients with PGR compared with PPR, in particular after 10 h of dexamethasone stimulation. These data were correlated with cell survival, demonstrating a more pronounced induction of apoptosis in cells from patients with PGR as compared with PPR. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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