PT  - JOURNAL ARTICLE
AU  - Liu, Zhiming
AU  - Hazan-Halevy, Inbal
AU  - Harris, David M.
AU  - Li, Ping
AU  - Ferrajoli, Alessandra
AU  - Faderl, Stefan
AU  - Keating, Michael J.
AU  - Estrov, Zeev
TI  - STAT-3 Activates NF-κB in Chronic Lymphocytic Leukemia Cells
AID  - 10.1158/1541-7786.MCR-10-0559
DP  - 2011 Apr 01
TA  - Molecular Cancer Research
PG  - 507--515
VI  - 9
IP  - 4
4099  - http://mcr.aacrjournals.org/content/9/4/507.short
4100  - http://mcr.aacrjournals.org/content/9/4/507.full
SO  - Mol Cancer Res2011 Apr 01; 9
AB  - NF-κB plays a major role in the pathogenesis of B-cell neoplasms. A broad array of mostly extracellular stimuli has been reported to activate NF-κB, to various degrees, in chronic lymphocytic leukemia (CLL) cells. Because CLL cells harbor high levels of unphosphorylated STAT-3 (USTAT-3) and USTAT-3 was reported to activate NF-κB, we sought to determine whether USTAT-3 activates NF-κB in CLL. Using the electrophoretic mobility shift assay (EMSA), we studied peripheral blood low-density cells from 15 patients with CLL and found that CLL cell nuclear extracts from all the samples bound to an NF-κB DNA probe, suggesting that NF-κB is constitutively activated in CLL. Immunoprecipitation studies showed that STAT-3 bound NF-κB p65, and confocal microscopy studies detected USTAT-3/NF-κB complexes in the nuclei of CLL cells, thereby confirming these findings. Furthermore, infection of CLL cells with retroviral STAT-3-short hairpin RNA attenuated the binding of NF-κB to DNA, as assessed by EMSA, and downregulated mRNA levels of NF-κB–regulated genes, as assessed by quantitative PCR. Taken together, our data suggest that USTAT-3 binds to the NF-κB p50/p65 dimers and that the USTAT-3/NF-κB complexes bind to DNA and activate NF-κB–regulated genes in CLL cells. Mol Cancer Res; 9(4); 507–15. ©2011 AACR.