title: Circadian-disruption-induced gene expression changes in rodent mammary tissues.
abstract: 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.
authors.affiliation: Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, Canada.
authors.forename: David Z
authors.initials: DZ
authors.lastname: Kochan
authors.affiliation: Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, Canada.
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Ilnytskyy
authors.affiliation: Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, Canada.
authors.forename: Andrey
authors.initials: A
authors.lastname: Golubov
authors.affiliation: Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, AB, Canada.
authors.forename: Scott H
authors.initials: SH
authors.lastname: Deibel
authors.affiliation: Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, AB, Canada.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: McDonald
authors.affiliation: Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, Canada.
authors.forename: Olga
authors.initials: O
authors.lastname: Kovalchuk
keywords: breast cancer; circadian disruption; transcriptome