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Title: Molecular characterization of the CGL1 (HeLa x Normal Fibroblast) human hybrid cell system and ionizing radiation induced segregants
Authors: Pirkkanen, Jake S.
Keywords: CGL1;hybrid cells;neoplastic transformation;ionizing radiation;transcriptomics;gene expression;carcinogenesis;microarray profiling;tumor suppressor gene
Issue Date: 3-Jul-2019
Abstract: Cellular neoplastic transformation assays have been utilized for many years as an in vitro method for assessing the effect of various stimuli on transformation frequency, and a variety of mouse and human cell systems have been generated for experimental use. The CGL1 cell system is a nontumorigenic pre-neoplastic human hybrid tissue cell model that was derived from the fusion of tumorigenic HeLa cervical cancer cells with non-tumorigenic normal human skin fibroblasts. It has been used for many decades to explore the effects of a variety of ionizing radiation types, doses and dose rates on neoplastic transformation rate. Additionally, irradiated segregants of CGL1 with contrasting tumorigenic phenotypes have been isolated and studied. The non-tumorigenic and tumorigenic segregants of the CGL1 system have been an excellent model for studying these effects in the context of neoplastic transformation. However, there have been few attempts in the last several decades to employ global gene expression technologies to further investigate these model cell segregants. The central goal of this thesis was to utilize modern transcriptomic array capabilities and molecular functional assay techniques to characterize the cell system at an unprecedented level in the context of genetic and molecular mechanisms. To this end, global human transcriptomic microarray technology was implemented to characterize the CGL1 cell system, including radiation induced segregants CON and GIM, as well as GIM cells re-expressing candidate tumor suppressor gene FRA1. This research elucidated significant differentially expressed genes, pathway level differences, putative upstream regulators and proposed mechanistic causal factors influencing differences between tumorigenic and non-tumorigenic segregants of the CGL1 model. Additionally, novel findings regarding the role of candidate tumor suppressor gene FRA1 have been discovered with respect to the mechanisms influencing an altered tumorigenic phenotype. The experimental work contained within this thesis brings this wellestablished model system of neoplastic transformation into a contemporary molecular light. These findings significantly update and contribute to our understanding of the mechanisms driving phenotypic differences between these cells in the context of tumorigenicity, and provide new information for future proposed research endeavors.
Appears in Collections:Biomolecular Sciences - Doctoral Theses
Doctoral Theses

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