Interleukin-6 acts as an antiapoptotic factor in human esophageal carcinoma cells through the activation of both STAT3 and mitogen-activated protein kinase pathways

Oncogene. 2003 Oct 30;22(49):7809-18. doi: 10.1038/sj.onc.1207084.


The production of interleukin-6 (IL-6) has been discovered in a variety of human tumors. Here we report the expression of IL-6, IL-6 receptor alpha (IL-6Ralpha), and gp130 in human esophageal carcinoma tissues. We further demonstrate that IL-6 protects an esophageal carcinoma cell line CE48T/VGH from apoptosis induced by staurosporine. IL-6 stimulation induced a rapid phosphorylation of gp130 and STAT3, and a dominant-negative STAT3 completely abolished the antiapoptotic effect. IL-6 also activated ERK 1/2 in CE48T/VGH cells. Inhibition of the ERK activation by PD98059 and transfection of a dominant-negative ERK2 completely blocked the protection of IL-6 against apoptosis. Thus, both STAT and MAP kinase pathways are responsible for the IL-6-delivered survival signal in human esophageal carcinoma cells. In contrast, PI3-K inhibitors only partially attenuated the effect of IL-6, suggesting that PI3-K does not play a major role in the antiapoptotic signal of IL-6 in our system. To investigate whether IL-6 could induce the production of antiapoptotic molecules, proteins of the Bcl-2 family were measured. While Bcl-2, Bcl-x(L,), and Bax were not affected, Mcl-1 was induced by IL-6 in human esophageal carcinoma cells. Our results suggest that IL-6 may contribute to the progression of esophageal cancers in an autocrine or paracrine manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Cell Division
  • Cell Line, Tumor
  • DNA-Binding Proteins / physiology*
  • Esophageal Neoplasms / pathology*
  • Humans
  • Interleukin-6 / analysis
  • Interleukin-6 / physiology*
  • Mitogen-Activated Protein Kinases / physiology*
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins / biosynthesis
  • Phosphatidylinositol 3-Kinases / physiology
  • Proto-Oncogene Proteins c-bcl-2*
  • Receptors, Interleukin-6 / analysis
  • STAT3 Transcription Factor
  • Signal Transduction*
  • Trans-Activators / physiology*


  • DNA-Binding Proteins
  • Interleukin-6
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Interleukin-6
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • Phosphatidylinositol 3-Kinases
  • Mitogen-Activated Protein Kinases