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WakerThesis.pdf (7.42 MB)
ETD Abstract Container
Abstract Header
Metabolic Characterization of MPNST Cell Lines
Author Info
Waker, Christopher A.
ORCID® Identifier
http://orcid.org/0000-0002-0787-5702
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=wright1433182427
Abstract Details
Year and Degree
2015, Master of Science (MS), Wright State University, Physiology and Neuroscience.
Abstract
Malignant transformation is the process by which cells develop cancer properties. While many causes for malignant transformation are known (i.e. common genetic mutations and/or exposure to toxins or viruses), the basic requirements that allow a cell to stay alive with altered nutrient and energy requirements are just now being studied. In some tumor types malignant cells undergo changes that result in metabolic differences compared to normal cells. These can include defects in mitophagy resulting in an accumulation of dysfunctional mitochondria and/or a metabolic switch resulting in increased glycolysis, termed the Warburg effect. Increased tumor growth and metastasis have also been associated with mitochondrial DNA mutations in some tumor types. In this study, we characterized the mitochondrial function of malignant peripheral nerve sheath tumor (MPNST) cell lines commonly used to study malignant transformation in Neurofibromatosis Type I. We identified metabolic differences between NF1-wildtype (STS26T) and NF1-deficient (ST88-14, 90-8, and S462) MPNST cell lines by measuring extracellular acidification and oxygen consumption, mitochondrial respiration protein expression, and ROS levels. Similar to findings from other malignant tumors, all MPNST cell lines were more glycolytic compared to non-tumorigenic normal human Schwann cells and surprisingly NF1-deficiency correlated with lower glycolytic and mitochondrial respiratory rate compared to wildtype MPNST. Mitochondrial respiratory rates and respiratory protein expression were significantly lower in the NF1-deficient MPNST cell lines when compared to NF1-wildtype MPNST cells. These findings demonstrate that neurofibromin affects glycolysis and mitochondrial respiration in malignant cells.
Committee
Debra Mayes, Ph.D. (Advisor)
Robert Putnam, Ph.D. (Committee Member)
Christopher Wyatt, Ph.D. (Committee Member)
Pages
105 p.
Subject Headings
Biomedical Research
;
Cellular Biology
;
Neurosciences
Keywords
Neurofibromatosis Type 1
;
malignant peripheral nerve sheath tumor
;
metabolism
;
glycolysis
;
oxidative phosphorylation
;
ROS
;
mitochondria
;
proton leak
;
NF1
;
Ras
;
Electron transport chain
;
Extracellular Flux
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Refworks
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Citations
Waker, C. A. (2015).
Metabolic Characterization of MPNST Cell Lines
[Master's thesis, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1433182427
APA Style (7th edition)
Waker, Christopher.
Metabolic Characterization of MPNST Cell Lines .
2015. Wright State University, Master's thesis.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=wright1433182427.
MLA Style (8th edition)
Waker, Christopher. "Metabolic Characterization of MPNST Cell Lines ." Master's thesis, Wright State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=wright1433182427
Chicago Manual of Style (17th edition)
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Document number:
wright1433182427
Download Count:
542
Copyright Info
© 2015, some rights reserved.
Metabolic Characterization of MPNST Cell Lines by Christopher A. Waker is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Wright State University and OhioLINK.