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Autocrine production of interleukin 6 causes multidrug resistance in breast cancer cells

  1. Author:
    Conze, D.
    Weiss, L.
    Regen, P. S.
    Bhushan, A.
    Weaver, D.
    Johnson, P.
    Rincon, M.

  2. Author Address

    Univ Vermont, Dept Med, Immunobiol Sect, Given Med Bldg D-305, Burlington, VT 05405 USA. Univ Vermont, Dept Med, Immunobiol Sect, Burlington, VT 05405 USA. Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. Idaho State Univ, Coll Pharm, Dept Pharmaceut Sci, Pocatello, ID 83209 USA. NCI, Eukaryot Transcript Regulat Sect, Regulat Cell Growth Lab, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. Rincon M Univ Vermont, Dept Med, Immunobiol Sect, Given Med Bldg D-305, Burlington, VT 05405 USA.
    1. Year: 2001
  2. Journal: Cancer Research
    1. 61
    2. 24
    3. Pages: 8851-8858
  4. Type of Article: Article
  1. Abstract:

    It has been shown that serum levels of interleukin (IL)-6 are elevated in patients with various types of cancer. However, the exact source of IL-6 in these patients and its role in tumor progression remain unclear. Here we demonstrate that the autocrine production of IL-6 by tumor cells promotes resistance of the cells to chemotherapy, a novel function of IL-6 in cancer biology. Breast cancer cells that are sensitive to drug treatment do not express IL-6, whereas high levels of IL-6 are produced by multidrug-resistant breast cancer cells. Expression of the IL-6 gene in drug-sensitive breast cancer cells increases their resistance to drug treatment by activating the CCAAT enhancer-binding protein family of transcription factors and inducing mdr1 gene expression. Thus, the autocrine production of IL-6 by tumor cells is an important factor in determining the susceptibility or resistance of these cells to drug treatment. Because tumors from some breast cancer patients contain IL-6-producing cells, it is possible that IL-6 could potentially be used as a prognostic factor for chemotherapy resistance.

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