Et Al., 1989; Reibnegger Et Survival Responses
Oncogene (2002) 21, 1391 ± 1400 ã 2002 Nature Publishing Group All rights reserved 0950 ± 9232/02 $25.00 www.nature.com/onc Role of the AKT kinase in expansion of multiple myeloma clones: eects on cytokine-dependent proliferative and survival responses Jung-hsin Hsu1, Yijiang Shi1, Liping Hu1, Myrna Fisher1, Thomas F Franke2 and Alan Lichtenstein*,1 1Department of Medicine and Pathology, West LA VA-UCLA Medical Center and Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California, CA 90073, USA; 2Department of Pharmacology, Columbia University, New York, NY 10032, USA IL-6 is an established growth factor for multiple bone marrow of myeloma patients and levels correlate myeloma tumor cells, stimulating proliferative and with disease activity (Bataille et al., 1989; Reibnegger et survival responses. Recent work indicates that IL-6 can al., 1991; (2) Monoclonal anti-IL-6 antibodies can activate the AKT kinase in myeloma cells. Thus, to test induce anti-tumor responses in patients (Klein et al., a potential role for AKT in IL-6-induced cellular 1991); Bataille et al., 1995), and; (3) IL-6 transgenic responses, we transfected myeloma cell lines with an mice are prone to developing MM (Suematsu et al., active `E40K' or dominant negative `PH' AKT construct 1992), while IL-6 knockout mice are resistant (Hilbert using an adenoviral vector. Transfection of the E40K et al., 1995). The source of IL-6 is from the marrow into myeloma cells resulted in enhanced tumor cell microenvironment which stimulates MM cells in a growth and expression of the PH dominant negative paracrine fashion (Klein et al., 1989).
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