Altering the ADIPO: LEP Ratio Secreted by Obese Adipose Tissue affects the Tumor Growth Microenvironment of MCF7 Breast Cancer Cells

Simple item page
dc.contributor.advisorConnor, Michael K.
dc.creatorTheriau, Christopher Frederick
dc.date.accessioned2017-07-27T12:37:13Z
dc.date.available2017-07-27T12:37:13Z
dc.date.copyright2016-11-04
dc.date.issued2017-07-27
dc.date.updated2017-07-27T12:37:13Z
dc.degree.disciplineKinesiology & Health Science
dc.degree.levelDoctoral
dc.degree.namePhD - Doctor of Philosophy
dc.description.abstractBreast cancer continues to be the number one cause of new cancer cases and second in mortality rate in Canadian women. For almost 50 years now researchers have shown a statistical link between obesity and breast cancer. Although adipose tissue in the past was considered an inert storage depot, we now know it produces and secretes the adipokines adiponectin (ADIPO) and leptin (LEP). Lean individuals have been shown to have higher circulating levels of ADIPO and lower levels of circulating LEP, while the opposite is found in obese individuals, 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, stabilizing the cell cycle inhibitor protein p27, leading to cell cycle arrest. Leptin on the other hand binds to its membrane receptor Ob-Rb and activates the Akt signaling pathway, increasing the cytoplasmic localization of p27, leading to cell proliferation. The purpose of this thesis was to look at altering this ADIPO:LEP ratio through diet, physical activity and nutraceutical methods to determine if an altered secretome secretion profile could alter the adipose-dependent effects of obesity on breast cancer cell proliferation. The results show that any intervention that led to an alteration of the ratio between ADIPO:LEP ultimately leads to varying degrees of cell cycle arrest in MCF7 breast cancer cells depending on diet, volume of physical activity and nutraceutical intervention. I show that regardless of menopausal status, the ADIPO:LEP ratio remained as a reliable and consistent predictor of the proliferative tumor growth microenvironment created by obese adipose tissue. Additionally, stabilizing ADIPO signaling through AdipoR1 abolishes the proliferative effects of an obese adipose-dependent growth microenvironment on breast cancer cells. The implications of this thesis is that adipose tissue presents a stable and predictable component of a patients physiology providing possible novel treatment avenues for obesity-linked cancers.
dc.identifier.urihttp://hdl.handle.net/10315/33438
dc.language.isoen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subjectMolecular biology
dc.subject.keywordsObesity
dc.subject.keywordsAdipose Tissue
dc.subject.keywordsBreast Cancer
dc.subject.keywordsPhysical Activity
dc.subject.keywordsAdiponectin
dc.subject.keywordsLeptin
dc.titleAltering the ADIPO: LEP Ratio Secreted by Obese Adipose Tissue affects the Tumor Growth Microenvironment of MCF7 Breast Cancer Cells
dc.typeElectronic Thesis or Dissertation

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Theriau_Christopher_F_2016_PhD.pdf
Size:
2.84 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 2 of 2
No Thumbnail Available
Name:
license.txt
Size:
1.83 KB
Format:
Plain Text
Description:
Download
No Thumbnail Available
Name:
YorkU_ETDlicense.txt
Size:
3.38 KB
Format:
Plain Text
Description:
Download

Collections

Kinesiology & Health Science

All items in the YorkSpace institutional repository are protected by copyright, with all rights reserved except where explicitly noted.