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

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Abstract

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 α (IL-6Rα), 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-xL,, 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.

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Acknowledgements

We thank Dr Jen-Ping Chang, Dr Pyng-Jing Lin, Dr Biing-Shiun Huang, Dr Yi-Ming Chen, and Dr Yi-Jen Chen for providing the surgical specimens. We also thank Dr Ming-Ji Fann and Dr Ruey-Hwa Chen for their valuable suggestions. We appreciate Ms Shiang-Lien Lu for her excellent secretarial assistance. This work was supported in part by Grants NSC88-2314-B075-013 from the National Science Council and VTY89-P5-45 from VTY Joint Research Program, Tsou's Foundation, Taiwan, Republic of China.

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Authors and Affiliations

  1. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China

    Chuen-Miin Leu & Cheng-po Hu

  2. Institute of Microbiology & Immunology, National Yang-Ming University, Taipei, Taiwan, Republic of China

    Chuen-Miin Leu, Chungming Chang & Cheng-po Hu

  3. Institute of Public Health, National Yang-Ming University, Taipei, Taiwan, Republic of China

    Fen-Hwa Wong

  4. Department of Intramural Research Affairs, National Health Research Institute, Taipei, Taiwan, Republic of China

    Chungming Chang

  5. Division of Molecular and Genomic Medicine, National Health Research Institute, Taipei, Taiwan, Republic of China

    Shiu-Feng Huang

  6. Department of Pathology, Chang Gung Memorial Hospital, Taipei, Taiwan, Republic of China

    Shiu-Feng Huang

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  1. Chuen-Miin Leu
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  2. Fen-Hwa Wong
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Correspondence to Cheng-po Hu.

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Leu, CM., Wong, FH., Chang, C. et al. 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 22, 7809–7818 (2003). https://doi.org/10.1038/sj.onc.1207084

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  • DOI: https://doi.org/10.1038/sj.onc.1207084

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