将代表血液系统恶性肿瘤的细胞系从糖皮质激素抵抗型转变为糖皮质激素敏感型：信号通路相互作用
Converting cell lines representing hematological malignancies from glucocorticoid-resistant to glucocorticoid-sensitive: signaling pathway interactions.
作者信息
Garza Anna S, Miller Aaron L, Johnson Betty H, Thompson E Brad
机构信息
The University of Texas Medical Branch, Department of Biochemistry and Molecular Biology, Galveston, TX 77555-1068, USA.
出版信息
Leuk Res. 2009 May;33(5):717-27. doi: 10.1016/j.leukres.2008.10.006. Epub 2008 Nov 13.
Abstract
Mitogen-activated protein kinases (MAPKs), protein kinase A (PKA) and mTOR pathways modulate the apoptotic effects of glucocorticoids (GCs) in human lymphoblastic leukemia CEM cells. We now show that manipulation of these pathways converts several cell lines, representing other lymphoid malignancies, from GC-resistant to GC-sensitive. Basal levels of phosphorylated JNK and ERK were elevated in the GC-resistant cells. Treatments that directly or indirectly reduced phosphorylated JNK and ERK resulted in Dex sensitivity in five resistant lymphoid cell lines. Sensitivity to GC-driven apoptosis correlated with GC-dependent increases in phosphorylated and total glucocorticoid receptor, and in increased levels of the pro-apoptotic protein Bim.
摘要
丝裂原活化蛋白激酶（MAPKs）、蛋白激酶A（PKA）和mTOR信号通路调节糖皮质激素（GCs）对人淋巴细胞白血病CEM细胞的凋亡作用。我们现在发现，对这些信号通路的调控可使代表其他淋巴系统恶性肿瘤的多种细胞系从GC抵抗转变为GC敏感。GC抵抗细胞中磷酸化JNK和ERK的基础水平升高。直接或间接降低磷酸化JNK和ERK的处理导致5种耐药淋巴样细胞系对地塞米松敏感。对GC诱导凋亡的敏感性与GC依赖性磷酸化和总糖皮质激素受体增加以及促凋亡蛋白Bim水平升高相关。
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