4.5 Article

Growth and fatty acid metabolism of human breast cancer (MCF-7) xenografts in nude rats: impact of constant light-induced nocturnal melatonin suppression

Journal

BREAST CANCER RESEARCH AND TREATMENT
Volume 79, Issue 3, Pages 313-320

Publisher

SPRINGER
DOI: 10.1023/A:1024030518065

Keywords

circadian disruption; constant light; fatty acids; MCF-7 human breast cancer xenografts; melatonin; pineal gland

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Funding

  1. NCI NIH HHS [R01 CA76197, R01 CA85408] Funding Source: Medline

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The nocturnal melatonin (MLT) surge is a relevant oncostatic signal for a variety of experimental malignancies. Population studies support the hypothesis that exposure to light at night may represent a new risk factor for breast cancer possibly through the suppression of pineal MLT production and/or circadian disruption. We tested the ability of constant light exposure to suppress MLT production in female nude rats and stimulate the growth of tissue-isolated MCF-7 human breast cancer xenografts via increased tumor linoleic acid (LA) metabolism. Rats maintained on an alternating light/dark cycle (L: D group) exhibited a robust circadian MLT rhythm that was abolished following constant light exposure. During the exposure of animals bearing tissue-isolated human MCF-7 breast cancer xenografts to constant light, the rate of tumor growth markedly increased relative to the L: D group. Tumor LA uptake and its metabolism to the mitogen 13-hydroxyoctadecadienoic acid (13-HODE) were also substantially higher under constant light conditions. This is the first biological evidence for a potential link between constant light exposure and increased human breast oncogenesis involving MLT suppression and stimulation of tumor LA metabolism.

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