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

doi:10.1016/j.leukres.2011.07.002

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 journal › Article › peer-review

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. 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) 2 inactivates GCs within cells. Here, we show the association between GC sensitivity and 11 beta-HSD2 expression in human T-cell leukemic cell lines. 11 beta-HSD2 mRNA and protein levels were considerably higher in GC-resistant MOLT4F cells than in GC-sensitive CCRF-CEM cells. The 11 beta-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 11 beta-HSD2 is a cause of GC-resistance in ALL. (C) 2011 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	1644-1648
Number of pages	5
Journal	Leukemia Research
Volume	35
Issue number	12
DOIs	https://doi.org/10.1016/j.leukres.2011.07.002
Publication status	Published - Dec 2011

Keywords / Materials (for Non-textual outputs)

Glucocorticoid resistance
11β-hydroxysteroid dehydrogenase 2
acute lymphoblastic leukemia

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10.1016/j.leukres.2011.07.002

Expression of 11beta-hydroxysteroid dehydrogenase 2 contributes to glucocorticoid resistance in lymphoblastic leukemia cellsAccepted author manuscript, 341 KB

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

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. 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) 2 inactivates GCs within cells. Here, we show the association between GC sensitivity and 11 beta-HSD2 expression in human T-cell leukemic cell lines. 11 beta-HSD2 mRNA and protein levels were considerably higher in GC-resistant MOLT4F cells than in GC-sensitive CCRF-CEM cells. The 11 beta-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 11 beta-HSD2 is a cause of GC-resistance in ALL. (C) 2011 Elsevier Ltd. All rights reserved.",

keywords = "Glucocorticoid resistance, 11β-hydroxysteroid dehydrogenase 2, acute lymphoblastic leukemia",

author = "Shuji Sai and Yuichi Nakagawa and Rie Yamaguchi and Masako Suzuki and Kimiyoshi Sakaguchi and Shuichi Okada and Seckl, {Jonathan R.} and Takehiko Ohzeki and Chapman, {Karen E.}",

year = "2011",

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T1 - Expression of 11beta-hydroxysteroid dehydrogenase 2 contributes to glucocorticoid resistance in lymphoblastic leukemia cells

AU - Sai, Shuji

AU - Nakagawa, Yuichi

AU - Yamaguchi, Rie

AU - Suzuki, Masako

AU - Sakaguchi, Kimiyoshi

AU - Okada, Shuichi

AU - Seckl, Jonathan R.

AU - Ohzeki, Takehiko

AU - Chapman, Karen E.

PY - 2011/12

Y1 - 2011/12

N2 - 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. 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) 2 inactivates GCs within cells. Here, we show the association between GC sensitivity and 11 beta-HSD2 expression in human T-cell leukemic cell lines. 11 beta-HSD2 mRNA and protein levels were considerably higher in GC-resistant MOLT4F cells than in GC-sensitive CCRF-CEM cells. The 11 beta-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 11 beta-HSD2 is a cause of GC-resistance in ALL. (C) 2011 Elsevier Ltd. All rights reserved.

AB - 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. 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) 2 inactivates GCs within cells. Here, we show the association between GC sensitivity and 11 beta-HSD2 expression in human T-cell leukemic cell lines. 11 beta-HSD2 mRNA and protein levels were considerably higher in GC-resistant MOLT4F cells than in GC-sensitive CCRF-CEM cells. The 11 beta-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 11 beta-HSD2 is a cause of GC-resistance in ALL. (C) 2011 Elsevier Ltd. All rights reserved.

KW - Glucocorticoid resistance

KW - 11β-hydroxysteroid dehydrogenase 2

KW - acute lymphoblastic leukemia

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U2 - 10.1016/j.leukres.2011.07.002

DO - 10.1016/j.leukres.2011.07.002

M3 - Article

SN - 0145-2126

VL - 35

SP - 1644

EP - 1648

JO - Leukemia Research

JF - Leukemia Research

IS - 12

ER -

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

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