Determining the Effect of Cryptochrome Loss and Circadian Clock Disruption on Tumorigenesis in Mice
Abstract
Circadian clock disruption may be correlated to increased risk of breast cancer in humans and has been linked to tumor progression and development in mice. We tested mice and cell lines lacking both the Cryptochrome 1 and Cryptochrome 2 circadian clock genes, rendering them arrhythmic. We find that arrhythmic Cryptochrome knockout mice and cells, respectively, are indistinguishable from wild-type controls with regard to ionizing radiation-induced morbidity and mortality and cell cycle checkpoint response, respectively. We confirm upregulation of the anti-mitotic kinase Wee1 as has been previously reported in Cryptochrome knockout liver tissue; however, there does not appear to be a functional consequence of this upregulation with regards to cell cycle checkpoint response. We find that c-Myc, which was reported to be upregulated in the absence of circadian gene Period 2, is unaffected by loss of Cryptochrome. We are currently investigating expression of other cell-cycle related genes in Cryptochrome knockout mouse tissues and cells. Our current results indicate that circadian clock disruption per se does not predispose mice to cancer; rather, the effects previously reported are likely due to contributions of individual clock proteins to damage response pathways.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2006
- Accession Number
- ADA452750
Entities
People
- Michele A. Gauger
Organizations
- University of North Carolina at Chapel Hill