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Requirement of ErbB2 for signalling by interleukin-6 in prostate carcinoma cells

Nature volume 393, pages 83–85 (1998)Cite this article

Abstract

Interleukin-6 (IL-6) is a cytokine that was initially recognized as a regulator of immune and inflammatory responses1, but it also regulates the growth of many tumour cells, including prostrate carcinoma2,3,4. Overexpression of the growth-factor receptors ErbB2/neu and ErbB3 has been implicated in the neoplastic transformation of prostate carcinoma5,6,7. Here we show that treatment of the prostate cancer cell line LNCaP with IL-6 induces tyrosine phosphorylation of ErbB2 and ErbB3, but not ErbB1/EGFR. We also show that ErbB2 forms a complex with the gp130 subunit of the IL-6 receptor in an IL-6-dependent manner. This association is important because the inhibition of ErbB2 activity results in abrogation of IL-6-induced MAPK activation. Thus ErbB2 is a critical component of IL-6 signalling through the MAP kinase pathway. These data show how a cytokine receptor can diversify its signalling pathways by engaging with a growth-factor receptor kinase.

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Figure 1: Association of ErbB2 and ErbB3 with Shc in response to IL-6 in LNCaP cells.
Figure 2: IL-6 stimulates the tyrosine phosphorylation of ErbB2 with rapid kinetics.
Figure 3: Co-precipitation of ErbB2 and gp130 in response to IL-6 stimulation in LNCaP.
Figure 4: AG879 and scFv5R block the MAP kinase activation and cell growth induced by IL-6.

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Acknowledgements

We thank N. E. Hynes for the scFv5R clone, J. Jacobberger and T. G. Pretlow for CWR22 cells, and A. W. Grasso and K. Everiss for reading the manuscript. This work was supported by NIH grants. Y.Q. is a recipient of an NCI research oncology training fellowship.

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Authors and Affiliations

  1. Department of Molecular Biology and Microbiology, Case Western Reserve University, School of Medicine, 10900 Euclid Avenue, Cleveland, 44106, Ohio, USA

    Yun Qiu, Lakshmeswari Ravi & Hsing-Jien Kung

  2. Molecular and Genomic Medicine Division, National Health Research Institutes, 128 Yen-Chiu Yuan Road, Sec2, Taipei, Taiwan

    Hsing-Jien Kung

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  1. Yun Qiu
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Correspondence to Hsing-Jien Kung.

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Qiu, Y., Ravi, L. & Kung, HJ. Requirement of ErbB2 for signalling by interleukin-6 in prostate carcinoma cells. Nature 393, 83–85 (1998). https://doi.org/10.1038/30012

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