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

被引：125

作者：

Jourdan, M

Veyrune, JL

De Vos, J

Redal, N

Couderc, G

Klein, B

机构：

[1] INSERM, U475, F-34197 Montpellier, France

[2] CHU Montpellier, Unit Cellular Therapy, F-34197 Montpellier, France

来源：

ONCOGENE | 2003年 / 22卷 / 19期

关键词：

myeloma; IL-6; apoptosis; Mcl-1;

D O I：

10.1038/sj.onc.1206423

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

收藏

页码：2950 / 2959

页数：10

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