IL-6 up-regulates mcl-1 in human myeloma cells through JAK / STAT rather than ras / MAP kinase pathway

Eur J Immunol. 1999 Dec;29(12):3945-50. doi: 10.1002/(SICI)1521-4141(199912)29:12<3945::AID-IMMU3945>3.0.CO;2-O.


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


  • 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