Autocrine production of interleukin 6 causes multidrug resistance in breast cancer cells.
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.
Conze
D
D
Section of Immunobiology, Department of Medicine, University of Vermont, Burlington, Vermont 05405, USA.
Weiss
L
L
Regen
P S
PS
Bhushan
A
A
Weaver
D
D
Johnson
P
P
Rincón
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000096:biosynthesis / Q000235:genetics; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division / Q000502:physiology; D018432:Drug Resistance, Multiple / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C497252:CEBPD protein, human; D015850:Interleukin-6; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta