Abstract
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-x(L) 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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / immunology*
-
Gene Expression Regulation, Neoplastic / immunology
-
Humans
-
Interleukin-6 / genetics
-
Interleukin-6 / immunology*
-
Janus Kinase 2
-
MAP Kinase Signaling System / immunology
-
Multiple Myeloma / genetics*
-
Multiple Myeloma / immunology*
-
Myeloid Cell Leukemia Sequence 1 Protein
-
Neoplasm Proteins / genetics
-
Neoplasm Proteins / immunology*
-
Protein-Tyrosine Kinases / genetics
-
Protein-Tyrosine Kinases / immunology*
-
Proto-Oncogene Proteins c-bcl-2*
-
Proto-Oncogene Proteins*
-
STAT3 Transcription Factor
-
Signal Transduction / immunology*
-
Trans-Activators / genetics
-
Trans-Activators / immunology*
-
Tumor Cells, Cultured
-
Up-Regulation / immunology
Substances
-
DNA-Binding Proteins
-
Interleukin-6
-
Myeloid Cell Leukemia Sequence 1 Protein
-
Neoplasm Proteins
-
Proto-Oncogene Proteins
-
Proto-Oncogene Proteins c-bcl-2
-
STAT3 Transcription Factor
-
STAT3 protein, human
-
Trans-Activators
-
Protein-Tyrosine Kinases
-
JAK2 protein, human
-
Janus Kinase 2