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A major role for Mcl-1 antiapoptotic protein in the IL-6-induced survival of human myeloma cells.

Abstract : Interleukin-6 (IL-6) is a major survival factor for malignant plasma cells involved in multiple myeloma. Using an RNase protection assay, we looked for gene expression of 10 anti- and proapoptotic Bcl-2-family proteins in 12 IL-6-dependent human myeloma cell lines (HMCL). A high Mcl-1 gene expression was found in all HMCLs and the other genes were variably expressed. Out of the 10 Bcl-2-family members, only the Mcl-1 gene was regulated by IL-6. Upon starvation of IL-6, Mcl-1 gene expression decreased in association with myeloma cell apoptosis and was upregulated after adding IL-6 again in association with myeloma cell survival. A constitutive Mcl-1 expression was induced with an Mcl-1-GFP retrovirus in two IL-6-dependent HMCLs. The Mcl-1 HMCLs have a marked reduced apoptosis upon IL-6 starvation compared to HMCLs transduced with control GFP retrovirus and may grow without adding IL-6. These data emphasize the major role of Mcl-1 antiapoptotic protein in the IL-6-induced survival of human myeloma cells.
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Submitted on : Wednesday, February 14, 2007 - 4:21:48 PM
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Michel Jourdan, Jean-Luc Veyrune, John De Vos, Nicole Redal, Guilhem Couderc, et al.. A major role for Mcl-1 antiapoptotic protein in the IL-6-induced survival of human myeloma cells.. Oncogene, Nature Publishing Group, 2003, 22 (19), pp.2950-9. ⟨10.1038/sj.onc.1206423⟩. ⟨inserm-00130855⟩

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