Janjic, Bratislav/M
(2012)
Analysis of the Level of Oxidative Phosphorylatin in Breast Cancer Cell Types.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Aim. Glycolysis is a cell metabolic process by which glucose is converted to pyruvate. Under aerobic conditions, pyruvate is further oxidized by the citric acid cycle and oxidative phosphorylation (OXPHOS) to CO2 and water. Under anaerobic conditions pyruvate is converted to lactate. Warburg first noted that cancer cells take up and metabolize glucose in excess of their bioenergetics and biosynthetic needs and produce more lactic acid in aerobic condition than normal cells. Our hypothesis was that cell lines originated from breast tumors have lower levels of oxidative phosphorylation compared to cell lines that originated from normal tissue. Moreover, we expected that tumor cell lines originated from highly aggressive tumors would have lower oxidative phosphorylation than the cell lines originated from less aggressive tumors and normal tissues.
Method. The change in cellular oxygen consumption rate (OCR) in the presence of pharmacological modulators is the most suitable measure of oxidative phosphorylation. The OCR was measured on basal-like, claudin-low, HER-2, luminal and normal cell types, each represented by different number of cell lines. OCR were measured first at base level and then after successive treatments with different pharmacological modulators. Basal OCR, total reserve capacity OCR and ATP-linked OCR were calculated for each cell line. The linear mixed effect regression was used to define the model that described the best association between each of these dependent variables and the cell types, controlling for other variables.
Conclusion. We found that there is no significant difference in oxidative phosphorylation among basal-like, claudin-low and normal cell types. However, HER-2 and luminal cell types, originated from less aggressive tumors with better clinical outcome, did show statistically significant higher levels of oxidative phosphorylation than other types (basal-like, claudin-low).
Public health significance. It has been shown that breast cancer is the most common cancer among women of almost all races and it had been recognized as a major public health problem. Understanding metabolic differences between breast cancer cells and normal cells and among different type of breast cancer cells might have significance in designing appropriate chemo-therapeutics and treatment procedures for patients with different types of breast cancers.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
29 June 2012 |
| Date Type: |
Completion |
| Defense Date: |
6 April 2012 |
| Approval Date: |
29 June 2012 |
| Submission Date: |
23 March 2012 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
46 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Biostatistics |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
oxidative phosphorylation, OCR, breast cancer cell lines, basal OCR, total reserve capacity, ATP-linked OCR |
| Date Deposited: |
29 Jun 2012 15:41 |
| Last Modified: |
19 Dec 2016 14:38 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/11545 |
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