LIGHT DURING DARKNESS AND BREAST CANCER PROGRESSION

描述（由申请人提供）：本研究的长期目标是

DESCRIPTION (provided by applicant): The long-term goal of this research is to determine if light, present during darkness, is a risk factor for breast cancer progression. People in industrialized nations are being exposed to more artificial light during the night and the rate of breast cancer is increasing. The pineal gland hormone melatonin, which inhibits experimental human breast cancer growth, is produced during darkness; light present during darkness suppresses melatonin synthesis. The hypothesis to be tested is: Light, of the appropriate intensity, duration, timing and wavelength, present during darkness, stimulates breast cancer progression via melatonin suppression and a resultant disinhibition of tumor linoleic acid (LA) uptake and metabolism. The first aim is to measure the dose-response effects of exposure of nude female rats, bearing tissue-isolated estrogen receptor (ER)+ and progesterone receptor (PgR)+ MCF-7 human breast cancer xenografts, to different intensities of white light during darkness, on melatonin suppression in relation to tumor growth, LA metabolism and the expression of related growth signal transduction molecules (i.e., ER and PgR, melatonin receptor and cAMP). The second aim is to determine the dose-response effects of exposure of nude rats bearing MCF-7 xenografis in comparison with those bearing ER/PgR- MDA-MB-23 1 human breast cancer xenografts to different intensities of white light on melatonin suppression in relation to tumor growth. The third aim is to determine whether melatonin replacement will prevent the stimulative of effects of white light exposure during darkness on tumor growth, LA metabolism and the expression of related tumor growth signal transduction molecules. The fourth aim will test the effects of the duration and timing of light exposure during darkness on tumor growth and growth signal transduction events. This research may lead to the elucidation of "light-at-night" in conjunction with dietary fat intake as a new risk factor for breast cancer progression and to novel preventative measures for lowering breast cancer risk by combining modifications of indoor lighting and dietary fat intake with melatonin supplementation.