Proteomic Map of ER+ Breast Cancer Cell Cycle

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dc.contributor.authorTenga, Milagros Janneten
dc.contributor.committeechairLazar, Iuliana M.en
dc.contributor.committeememberSible, Jill C.en
dc.contributor.committeememberHelm, Richard F.en
dc.contributor.committeememberWalker, Richard A.en
dc.contributor.departmentBiologyen
dc.date.accessioned2017-04-06T15:42:22Zen
dc.date.adate2012-06-07en
dc.date.available2017-04-06T15:42:22Zen
dc.date.issued2012-05-01en
dc.date.rdate2016-10-18en
dc.date.sdate2012-05-06en
dc.description.abstractCancer is characterized by a deregulation of the cell cycle resulting in abnormal proliferation of cells that can bypass tightly regulated molecular checkpoints. Breast cancer is the most common cancer diagnosed in women, ~70% of cases displaying an estrogen receptor positive (ER+) phenotype. The aim of the present work was to generate a comprehensive overview of the biological mechanisms, molecular pathways and specific proteins involved in cell cycle progression in ER+ breast cancer cells. We focused on the G1-to-S phase transition of the cell cycle because major differences in cell proliferation mechanisms between normal and cancerous cells are observed at this point. We developed a large-scale proteomics strategy to enable the comparison of MCF-7 ER+ (cancer) and MCF-10A (non-tumorigenic) epithelial breast cells. Samples were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) followed by a label-free quantitation approach, i.e., spectral counting, for differential protein expression analysis. The study was divided into three distinct parts: 1) qualitative profiling of MCF-7 cells arrested in the G1-phase and released into the S-phase of the cell cycle, 2) differential expression profiling of MCF-7 cells in G1 and S, and 3) differential expression profiling of the G1-phases of MCF-7 and MCF-10A cells. The qualitative evaluation of MCF-7 proteomic data resulted in the identification of >2700 proteins (p-score<0.001). A large number of these proteins were involved in cell cycle relevant processes, being representative of all hallmarks of cancer. Differential expression analysis of the MCF-7 G1 and S-phases resulted in the identification of >250 proteins with roles in DNA repair, transcription, translation, chromatin maintenance and signaling. The MCF-7/MCF-10 comparison revealed that major cellular processes that require DNA access, such as the ones identified in the MCF-7 analysis, are up-regulated in the nucleus of MCF-7 cells during starvation, possibly allowing these cancerous cells to bypass the restriction point. Several proliferative and anti-proliferative markers were identified in both MCF-7 and MCF-10A cells.en
dc.description.degreePh. D.en
dc.identifier.otheretd-05062012-035226en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-05062012-035226/en
dc.identifier.urihttp://hdl.handle.net/10919/77066en
dc.language.isoen_USen
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectbreast canceren
dc.subjectmass spectrometryen
dc.subjectcell cycleen
dc.subjectproteomicsen
dc.titleProteomic Map of ER+ Breast Cancer Cell Cycleen
dc.typeDissertationen
dc.type.dcmitypeTexten
thesis.degree.disciplineBiologyen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en

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