| Title | Differential regulation of 11beta-hydroxysteroid dehydrogenase-1 by dexamethasone in glucocorticoid-sensitive and -resistant childhood lymphoblastic leukemia. |
| Publication Type | Journal Article |
| Year of Publication | 2009 |
| Authors | Sai S, Nakagawa Y, Sakaguchi K, Okada S, Takahashi H, Hongo T, Seckl JR, Chapman KE, Ohzeki T |
| Journal | Leukemia research |
| Volume | 33 |
| Issue | 12 |
| Pagination | 1696-8 |
| Date Published | 2009 Dec |
| ISSN | 1873-5835 |
| Keywords | 11-beta-Hydroxysteroid Dehydrogenase Type 1, Adolescent, Child, Child, Preschool, Dexamethasone, Female, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Humans, Infant, Male, Precursor Cell Lymphoblastic Leukemia-Lymphoma, RNA, Messenger |
| Abstract | 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. |
| Alternate Journal | Leuk. Res. |
| Refereed Designation | Refereed |
