Investigating the effect of circadian rhythm regulator Bmal1 on tumorigenesis in APCmin/- mice
Type of Proposal
Visual Presentation (Poster, Installation, Demonstration)
Faculty
Faculty of Science
Faculty Sponsor
Phillip Karpowicz
Proposal
Colorectal cancer is the second most commonly diagnosed cancer in Canada and among top three leading causes of cancer deaths. The rate of colorectal cancer is especially increased when the familial adenomatous polyposis coli (APC) gene is mutated. The APCmin/- mouse, which carries a heterozygous mutation of the Apc gene, is prone to polyp and tumour formation in the intestine, making it a valuable model for studying colorectal cancer. The circadian rhythm contributes to a host of physiological activities in mammals, including sleep-wake cycle and immune response. It is also thought to play a role in cellular processes, such as cell proliferation and differentiation. On a molecular level, the ‘rhythm’ is maintained by various negative feedback loops, leading to oscillating transcript and protein levels of several core clock genes, such as BMAL1, CLOCK, CRY 1-2 and PER 1-3. Recent studies show that dysfunction of circadian rhythm is implicated in colorectal cancer. For instance, abnormal levels of clock gene transcripts are found in more aggressive tumours and associated with worse disease prognosis. However, the precise mechanisms by which clock genes affect tumorigenesis are unclear. To investigate this issue, we knocked out BMAL1 to disrupt the circadian rhythm in Apc mutant mice. We used Apcmin/-Bmal1-/- and Apcmin/-Bmal1+/+ mice and synchronized their clock activity with a 12-hour light/12-hour dark photoperiod. Both genotypes of mice had significant polyp formations, as predicted given the Apc mutation. However, the Apcmin/-Bmal1-/- mice had twice as many tumours than the controls, throughout the small intestine. There are many potential explanations for this result, including an increase in cell proliferation, decrease in apoptosis, or dysregulation of cell differentiation, when the gene Bmal1-/- is absent. My project will use markers of these cellular activities to distinguish the role of BMAL in these processes.
Start Date
22-3-2018 2:30 PM
End Date
22-3-2018 4:30 PM
Location
Atrium
Investigating the effect of circadian rhythm regulator Bmal1 on tumorigenesis in APCmin/- mice
Atrium
Colorectal cancer is the second most commonly diagnosed cancer in Canada and among top three leading causes of cancer deaths. The rate of colorectal cancer is especially increased when the familial adenomatous polyposis coli (APC) gene is mutated. The APCmin/- mouse, which carries a heterozygous mutation of the Apc gene, is prone to polyp and tumour formation in the intestine, making it a valuable model for studying colorectal cancer. The circadian rhythm contributes to a host of physiological activities in mammals, including sleep-wake cycle and immune response. It is also thought to play a role in cellular processes, such as cell proliferation and differentiation. On a molecular level, the ‘rhythm’ is maintained by various negative feedback loops, leading to oscillating transcript and protein levels of several core clock genes, such as BMAL1, CLOCK, CRY 1-2 and PER 1-3. Recent studies show that dysfunction of circadian rhythm is implicated in colorectal cancer. For instance, abnormal levels of clock gene transcripts are found in more aggressive tumours and associated with worse disease prognosis. However, the precise mechanisms by which clock genes affect tumorigenesis are unclear. To investigate this issue, we knocked out BMAL1 to disrupt the circadian rhythm in Apc mutant mice. We used Apcmin/-Bmal1-/- and Apcmin/-Bmal1+/+ mice and synchronized their clock activity with a 12-hour light/12-hour dark photoperiod. Both genotypes of mice had significant polyp formations, as predicted given the Apc mutation. However, the Apcmin/-Bmal1-/- mice had twice as many tumours than the controls, throughout the small intestine. There are many potential explanations for this result, including an increase in cell proliferation, decrease in apoptosis, or dysregulation of cell differentiation, when the gene Bmal1-/- is absent. My project will use markers of these cellular activities to distinguish the role of BMAL in these processes.