地塞米松对糖皮质激素敏感和耐药的儿童淋巴细胞白血病中11β-羟类固醇脱氢酶-1的差异调节
Differential regulation of 11beta-hydroxysteroid dehydrogenase-1 by dexamethasone in glucocorticoid-sensitive and -resistant childhood lymphoblastic leukemia.
作者信息
Sai Shuji, Nakagawa Yuichi, Sakaguchi Kimiyoshi, Okada Shuichi, Takahashi Hiroyoshi, Hongo Teruaki, Seckl Jonathan R, Chapman Karen E, Ohzeki Takehiko
机构信息
Department of Pediatrics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
出版信息
Leuk Res. 2009 Dec;33(12):1696-8. doi: 10.1016/j.leukres.2009.04.016. Epub 2009 May 14.
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.
糖皮质激素疗法是儿童急性淋巴细胞白血病（ALL）至关重要的一线治疗方法。然而，糖皮质激素抵抗是一个治疗难题，其分子机制尚不清楚。11β-羟基类固醇脱氢酶-1（11β-HSD1）在糖皮质激素靶组织中表达，在该组织中它可将惰性的11-酮糖皮质激素再生为活性糖皮质激素，从而放大细胞内糖皮质激素水平。在此，我们展示了11β-HSD1在ALL患者（n = 14）白血病细胞中的表达情况。在糖皮质激素敏感和耐药的ALL细胞之间，糖皮质激素对11β-HSD1的调节存在差异。地塞米松可增加糖皮质激素敏感ALL细胞中11β-HSD1的mRNA水平，但在耐药组中则降低其水平。我们的数据表明，11β-HSD1的差异诱导作用与白血病中糖皮质激素敏感性有关。
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