A major role for Mcl-1 antiapoptotic protein in the IL-6-induced survival of human myeloma cells.
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.
Jourdan
Michel
M
INSERM U475 and Unit for Cellular Therapy, CHU Montpellier, 34197 Montpellier, France.
Veyrune
Jean-Luc
JL
De Vos
John
J
Redal
Nicole
N
Couderc
Guilhem
G
Klein
Bernard
B
D000906:Antibodies / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival / Q000502:physiology*; D050822:Cytokine Receptor gp130; D005822:Genetic Vectors; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D000906:Antibodies; D015703:Antigens, CD; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050822:Cytokine Receptor gp130