IL‐6 up‐regulates Mcl‐1 in human myeloma cells through JAK / STAT rather than Ras / MAP kinase pathway

Mcl‐1 is an anti‐apoptotic member of the Bcl‐2 family which is tightly regulated during myeloid and B cell differentiation. We have recently reported that Mcl‐1 is expressed in human myeloma cells and that Mcl‐1 and Bcl‐xL expression are correlated. In the current study, we demonstrate that IL‐6, a survival factor for the human myeloma cell line MDN, rapidly up‐regulates Mcl‐1 whereas it has no effect on Bcl‐2 protein level. In MDN cells, IL‐6 induces both extracellular signal‐regulated protein kinase (ERK)1,2 and STAT3 activation whereas STAT1 and STAT5 activation remains undetectable. Furthermore, while investigating the IL‐6 signaling pathway leading to Mcl‐1 up‐regulation, we show that a janus kinase (JAK)‐2 inhibitor is able to inhibit both STAT3 activation and Mcl‐1 up‐regulation whereas an MAP/ERK kinase (MEK) inhibitor has no effect. In conclusion, our data suggest the involvement of the JAK / STAT pathway but not of the Ras / mitogen‐activated protein (MAP) kinase pathway in IL‐6‐induced Mcl‐1 up‐regulation.

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