Overexpression of survivin in primary ATL cells and sodium arsenite induces apoptosis by down-regulating survivin expression in ATL cell lines
Overexpression of survivin in primary ATL cells and sodium arsenite induces apoptosis by down-regulating survivin expression in ATL cell lines
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DOI：
10.1182/blood-2005-08-3423
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发表时间：
2006-06-15
期刊：
影响因子：
20.3
通讯作者：
Akiyama, Shin-ichi
中科院分区：
文献类型：
--
作者：
Che, Xiao-Fang;Zheng, Chun-Lei;Akiyama, Shin-ichi
Patients with acute- or lymphoma-type adult T-cell leukemia (ATL) have a poor outcome because of the intrinsic drug resistance to chemotherapy. Protection from apoptosis is a common feature involved in multidrug-resistance of ATL. IAP (inhibitor of apoptosis) family proteins inhibit apoptosis induced by a variety of stimuli. In this study, we investigated the expression of IAP family members (survivin, cIAP1, cIAP2, and XIAP) in the primary leukemic cells from patients with ATL. We found that survivin was overexpressed in ATL, especially in acute-type ATL. Sodium arsenite was shown to down-regulate the expression of survivin at both the protein and RNA levels in a time- and dose-dependent manner, thus inhibiting cell growth, inducing apoptosis, and enhancing the caspase-3 activity in ATL cells. Nuclear factor-kappa B (NF-kappa B) enhances the transcriptional activity of survivin. Sodium arsenite suppressed the constitutive NF-kappa B activation by preventing the I kappa B-alpha, degradation and the nuclear translocation of NF-kappa B. These findings suggest that survivin is an important antiapoptotic molecule that confers drug resistance on ATL cells. Sodium arsenite was shown to down-regulate the expression of survivin through the NF-kappa B pathway, thus inhibiting cell growth and promoting apoptosis of ATL cells.
