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Streaming Media

Abstract

Changes in modern lifestyle such as lack of sleep, stress, and light exposure late at night are associated with increased rates of breast cancer. Most physiological processes, including growth, development, and metabolism, are controlled by circadian clocks. Circadian clocks respond to environmental cues to synchronize internal physiological processes, and thus, the disruption of this system may be responsible for this connection. The master clock in the brain coordinates peripheral circadian clocks located in every tissue of the body, including the mammary gland, and the core circadian component CLOCK regulates circadian oscillation of gene expression. Currently, the physiological function of the mammary clock, and the role of CLOCK in mammary cell growth and differentiation, are unknown. Our objective was to determine if the molecular clock controls mammary epithelial cell growth. shRNA specific for Clock was transfected into a normal mouse mammary epithelial cell line, HC-11. Q-PCR and western blot analysis showed shClock transfection significantly reduced Clock mRNA and protein abundance. Temporal analysis of molecular clock gene Per1 showed loss of circadian oscillation in shClock transfected cells, indicating loss of molecular clock function. Cyclin D1 (Ccnd1) expression was elevated in shClock transfected cells, and growth curve analysis revealed that shClock transfected cells had significantly shorter doubling time than HC-11 control cells. These findings support that CLOCK regulates mammary epithelial cell growth and suggests that disruption of circadian clock mechanisms may lead to cancer by altering cell growth regulation.

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Video abstract produced by undergraduate student LaQuan Lunford in a fall 2014 course from Purdue University’s Film and Video Studies program.

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