Expression of 11beta-hydroxysteroid dehydrogenase 2 contributes to glucocorticoid resistance in lymphoblastic leukemia cells

Shuji Sai, Yuichi Nakagawa, Rie Yamaguchi, Masako Suzuki, Kimiyoshi Sakaguchi, Shuichi Okada, Jonathan R. Seckl, Takehiko Ohzeki, Karen E. Chapman

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1644-1648
Number of pages5
JournalLeukemia Research
Volume35
Issue number12
DOIs
Publication statusPublished - Dec 2011
Externally publishedYes

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