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Disruption of the Circadian Rhythms of Gene Expression and the Development of Breast Cancer

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Annual rept. 15 Jan 2006-14 Jan 2007

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This project uses a mouse model to examine the effects of shiftwork on the expression of genes that are directly involved in the genesis and progression of breast cancer. Task 1 Shift work simulation experiments in mice have been accomplished. High variability has made it advisable to increase the number of animals from n5 per group to n10. Results show that shift work produces a shift in the rhythm of core clock genes and the attenuation of expression of genes involved in cell cycle. A manuscript with these results is currently in preparation. Task 2 Two preliminary experiments have been carried out to assess the grafting success of MCF-7 and MDA-MB-231 tumour cells. We expect to run the full experiment within 8 weeks. Task 4 We have successfully crossed the Clock mutation on to a BALBc-Foxn1nu background. The pups from this cross were not viable due to the inability of the mothers to lactate their offspring. This, in itself, is a very interesting finding. We have been able to maintain this colony by cross fostering the mutant pups to a lactating heterozygote mother. As a backup we have started to cross the Clock mutation on to a Severe combined immuno-defficient SCID mouse background with the expectation that these will not manifest the same problems.

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  • Medicine and Medical Research

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