Expression of 11beta-hydroxysteroid Dehydrogenase 2 Contributes to Glucocorticoid Resistance in Lymphoblastic Leukemia Cells

Overview

Journal Leuk Res

Date 2011 Jul 29

PMID 21794917

Citations 14

Authors

Shuji Sai

Yuichi Nakagawa

Rie Yamaguchi

Masako Suzuki

Kimiyoshi Sakaguchi

Shuichi Okada

Jonathan R Seckl

Takehiko Ohzeki

Karen E Chapman

Affiliations

Soon will be listed here.

Abstract

Synthetic glucocorticoids (GCs) form a crucial first-line treatment for childhood acute lymphoblastic leukemia (ALL). However prolonged GC therapy frequently leads to GC-resistance with an unclear molecular mechanism. 11β-hydroxysteroid dehydrogenase (11β-HSD) 2 inactivates GCs within cells. Here, we show the association between GC sensitivity and 11β-HSD2 expression in human T-cell leukemic cell lines. 11β-HSD2 mRNA and protein levels were considerably higher in GC-resistant MOLT4F cells than in GC-sensitive CCRF-CEM cells. The 11β-HSD inhibitor, carbenoxolone pre-treatment resulted in greater cell death with prednisolone assessed by methyl-thiazol-tetrazolium assay and caspase-3/7 assay, suggesting that 11β-HSD2 is a cause of GC-resistance in ALL.

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