The utilization of high-throughput -omics strategies, such as proteomics, in the analysis of breast
cancer will function to define central molecular characteristics across a disease that is associated
with a high degree of molecular heterogeneity. Data reported herein details the investigation of
key subjects in breast cancer biology focused on the characterization of endogenous and
experimentally-induced disease biology characteristics utilizing the application of LC-MS based
proteomic analyses of both in vitro models of breast cancer as well as primary clinical samples.
Results include a combined global and functional proteomic strategy to identify governing
functional roles for mutually, differentially abundant proteins observed across three divergent
cell line models of breast cancer. Further, evidence is presented which provides insights into the
regulatory activity of the breast cancer-associated microRNA (miR-145) in several cell line
models of breast cancer in which expression of this microRNA has been restored. Lastly, robust
analyses are detailed focused on the identification of differential protein characteristics indicative
of disease stage as well as of recurrent disease in breast cancer derived from proteomic analysis
of formalin-fixed, paraffin embedded (FFPE) clinical samples. These studies contribute to the
field of proteomics in the form of 1) providing robust experimental workflows directed towards
investigation of functional themes and associated functional targets in large protein data sets 2)
detailing strategies for navigating the application of proteomic analysis to microRNA target
discovery and 3) further development and utilization of methodologies towards the proteomic
analysis of clinical, FFPE tissue samples. Furthermore, these studies benefit the breast cancer
community on several fronts including 1) the elucidation of provocative protein candidates
which warrant further investigation for their role in regulating disease mechanisms underlying
v
breast cancer biology and 2) through the discovery of diagnostic markers indicative of discrete
subtypes and stages of disease progression in breast cancer. The results reported herein detail
disease-specific protein abundance characteristics associated with neoplastic progression in
breast cancer that will benefit further expansion of the basic biological understanding of this
disease and describes novel proteins for further evaluation as biomarker candidates for the
diagnosis of breast cancer.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-12162010-161345 |
| Date | 17 December 2010 |
| Creators | Bateman, Nicholas William |
| Contributors | Saleem A. Khan, Thomas P. Conrads, Bruce A. Freeman, Christopher Bakkenist, Rohit Bhargava |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-12162010-161345/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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