Interleukin 6 stimulates the production of immunoreactive endothelin 1 in human breast cancer cells.
To investigate the potential regulation of endothelin 1 production in human breast cancer cells, we measured the release of immunoreactive endothelin 1 (ir-ET-1) from the MCF-7 and ZR-75-1 breast cancer cell lines in response to various agents including estrogen and tamoxifen as well as several cytokines. ir-ET-1 was detected in conditioned medium of MCF-7 cells and ZR-75-1 cells by specific radioimmunoassay. Among the agents tested, estrogen, tamoxifen, tumor necrosis factor, gamma-interferon, interleukin (IL) 1, and transforming growth factor beta had no effect on ir-ET-1 secretion by these breast cancer cells. However, IL-6 (20 ng/ml) treatment of MCF-7 cells and ZR-75-1 cells caused maximal increases in the amount of ir-ET-1 secreted into the culture medium to 206 and 314% of basal values after 6 h, respectively. This effect of IL-6 on ir-ET-1 secretion was inhibited by actinomycin D and cycloheximide, indicating that IL-6 stimulates de novo synthesis of ir-ET-1 at a transcriptional level. Reverse-phase high performance liquid chromatography coupled with radioimmunoassay in the conditioned medium from IL-6-treated cells revealed one major ir-ET-1 component corresponding to human standard ET-1. The present study demonstrates the potential for IL-6 to stimulate ir-ET-1 production in human breast cancer cells, which may participate in the process of acute phase reactant-like expression of this peptide and/or in the process of IL-6 enhanced breast cancer cell motility, the latter being recently clarified.
Yamashita
J
J
Department of Surgery II, Kumamoto University Medical School, Japan.
Ogawa
M
M
Nomura
K
K
Matsuo
S
S
Inada
K
K
Yamashita
S
S
Nakashima
Y
Y
Saishoji
T
T
Takano
S
S
Fujita
S
S
D001943:Breast Neoplasms / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D016232:Endothelins / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016207:Cytokines; D016232:Endothelins; D004967:Estrogens; D015850:Interleukin-6; D013629:Tamoxifen; D003609:Dactinomycin; D003513:Cycloheximide