Regulation of ADIPOR1 function and signaling by adipokines in breast cancer MCF7 cells

"Breast cancer continues to be the number one cause of new cancer cases and second in mortality rate in Canadian women. For over 40 years researchers have shown a statistical link between obesity and breast cancer. Obesity has been linked to many non-communicable diseases but researchers are now showing several cancers are linked to obesity, including breast. Specifically, post-menopausal women are at increased risk to developing and dying from breast cancer with increased adipose ""fat"" tissue. Although adipose tissue in the past was considered an inert storage depot, we now know it produces and secretes the adipokines adiponectin and leptin. Lean individuals have been shown to have higher circulating levels of adiponectin and lower levels of circulating leptin, which ultimately alters the ratio between the two adipokines. Adiponectin has been shown to bind to its membrane receptor ADIPOR1 and activate the cell signalling pathway AMPK which directly stabilizes the cell cycle inhibitor protein p27. The effects of both adiponectin and leptin on ADIPOR1 have yet to be shown. Therefore the purpose of this thesis was to look at ADIPOR1 function, stability and regulation in order to determine what affects both adiponectin and leptin have on ADIPOR1. The results show that adiponectin is able to increase ADIPOR1 protein content while increases the amount of pAMPK and decreasing the amount of pAkt. I also show that upregulating ADIPOR1 can overcome the deleterious effects of LEP treatment and a HFD/obesity on cell cycle regulating proteins."