Honors College Thesis


Circadian Dysregulation is Associated with Alterations in Tumor Suppressor Activity in Murine Mammary Tissue Public Deposited

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  • Breast cancer is the second most common cancer among women in the US, however, only a small fraction of cases are attributable to heritable genetic mutations; the bulk arises from various behavioral and environmental factors. Loss of functional p53 is observed in over 50% of cases, and its activity relies on post-translational acetylation or deacetylation by various cellular proteins. SIRT1 is a class III HDAC that can remove the activating acetyl moiety. In a normal cell, stress activates p53, which then transcribes Hic1. HIC1 represses transcription of Sirt1 to prevent it from deactivating P53 by removing its acetyl group. Hic1 is epigenetically regulated, and hypermethylation of the Hic1 promoter can result in silencing of its expression. Previous work in our lab demonstrated increased methylation in the promoter region of Hic1 in mammary tissue derived from mice exposed to extended light at night (LAN) Due to an established link between SIRT1 and the regulation of the circadian rhythm, the present study explores the abundance of P53, SIRT1, and phosphorylated SIRT1 (p-SIRT1) in response to circadian dysregulation. Our results indicate a unique abundance pattern of SIRT1 and P53 in normal murine mammary tissue as well as alterations in P53, SIRT1, and p-SIRT1 abundance after a three-week period of exposure to LAN.
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