title: Differential regulation of 11beta-hydroxysteroid dehydrogenase-1 by dexamethasone in glucocorticoid-sensitive and -resistant childhood lymphoblastic leukemia.
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.
authors.affiliation: Department of Pediatrics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan. sshuji@hama-med.ac.jp
authors.forename: Shuji
authors.initials: S
authors.lastname: Sai
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Kimiyoshi
authors.initials: K
authors.lastname: Sakaguchi
authors.forename: Shuichi
authors.initials: S
authors.lastname: Okada
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Teruaki
authors.initials: T
authors.lastname: Hongo
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Seckl
authors.forename: Karen E
authors.initials: KE
authors.lastname: Chapman
authors.forename: Takehiko
authors.initials: T
authors.lastname: Ohzeki
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D003907:Dexamethasone; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1