Circadian-disruption-induced gene expression changes in rodent mammary tissues
David Z. Kochan1, Yaroslav Ilnytskyy1, Andrey Golubov1, Scott H. Deibel2, Robert J. McDonald2, Olga Kovalchuk1
1 Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, Canada
2 Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, AB, Canada
Olga Kovalchuk, email:
Keywords: circadian disruption, breast cancer, transcriptome
Received: November 24, 2015 Accepted: January 22, 2016 Published: February 12, 2016
Evidence is mounting that circadian disruption (CD) is a potential carcinogen in breast cancer development. However, despite the growing concern, to our knowledge, no studies have attempted a genome-wide analysis of CD-induced gene expression changes in mammary tissues. Using a rodent model system, a proven photoperiod-shifting paradigm, varying degrees of CD, and Illumina sequencing, we performed an exploratory genome-wide mRNA analysis in mammary tissues. Even though our analysis did not identify any significant patterns in mRNA levels based on the degree of CD, and the majority of groups did not show changes in gene expression on a large-scale, one group (two-week chronic ZT19) displayed 196 differentially expressed genes, 51 of which have been linked to breast cancer. Through gene-specific pathway analysis, the data illustrate that CD may promote breast cancer development through downregulation of DNA repair and p53 signaling pathways, thus promoting genomic instability and cancer development. Although these results have to be interpreted with caution because only a single group illustrated drastic changes in transcript levels, they indicate that chronic CD may directly induce changes in gene expression on a large-scale with potentially malignant consequences.