Overexpression of survivin in primary ATL cells and sodium arsenite induces apoptosis by down-regulating survivin expression in ATL cell lines.

نویسندگان

  • Xiao-Fang Che
  • Chun-Lei Zheng
  • Satsuki Owatari
  • Masato Mutoh
  • Takenari Gotanda
  • Hei-Cheul Jeung
  • Tatsuhiko Furukawa
  • Ryuji Ikeda
  • Masatatsu Yamamoto
  • Misako Haraguchi
  • Naomichi Arima
  • Shin-ichi Akiyama
چکیده

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-kappaB (NF-kappaB) enhances the transcriptional activity of survivin. Sodium arsenite suppressed the constitutive NF-kappaB activation by preventing the IkappaB-alpha degradation and the nuclear translocation of NF-kappaB. 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-kappaB pathway, thus inhibiting cell growth and promoting apoptosis of ATL cells.

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down-regulating survivin expression in ATL cell Overexpression of survivin in primary ATL cells and sodium arsenite

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عنوان ژورنال:
  • Blood

دوره 107 12  شماره 

صفحات  -

تاریخ انتشار 2006