Differential regulation of 11β-hydroxysteroid dehydrogenase-1 by dexamethasone in glucocorticoid-sensitive and -resistant childhood lymphoblastic leukemia
✍ Scribed by Shuji Sai; Yuichi Nakagawa; Kimiyoshi Sakaguchi; Shuichi Okada; Hiroyoshi Takahashi; Teruaki Hongo; Jonathan R. Seckl; Karen E. Chapman; Takehiko Ohzeki
- Publisher
- Elsevier Science
- Year
- 2009
- Tongue
- English
- Weight
- 251 KB
- Volume
- 33
- Category
- Article
- ISSN
- 0145-2126
No coin nor oath required. For personal study only.
✦ Synopsis
Glucocorticoid therapy forms a crucial first-line treatment for childhood acute lymphoblastic leukemia (ALL). However, glucocorticoid resistance is a therapeutic problem with an unclear molecular mechanism. 11beta-Hydroxysteroid dehydrogenase-1 (11beta-HSD1) is expressed in glucocorticoid target tissue, where it regenerates active glucocorticoids from inert 11keto-glucocorticoids, amplifying intracellular glucocorticoid levels. Here, we show 11beta-HSD1 expression in leukemic cells from ALL patients (n=14). 11beta-HSD1 was differentially regulated by glucocorticoids between glucocorticoid-sensitive and -resistant ALL cells. Dexamethasone increased 11beta-HSD1 mRNA levels in glucocorticoid-sensitive ALL cells, but decreased levels in the resistant group. Our data suggest that differential induction of 11beta-HSD1 contributes to the glucocorticoid sensitivity in leukemia.