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THE ROLE OF ESE-1 IN NON-SMALL CELL LUNG CANCER (NSCLC) CELLS

dc.contributor.advisorLee, Seong-Hoen_US
dc.contributor.authorLou, Zhiyuanen_US
dc.date.accessioned2021-02-13T06:30:18Z
dc.date.available2021-02-13T06:30:18Z
dc.date.issued2020en_US
dc.identifierhttps://doi.org/10.13016/9oa0-uc7f
dc.identifier.urihttp://hdl.handle.net/1903/26697
dc.description.abstractLung cancer is the most life-threatening cancer in the world. The identification of the effective molecular target is essential for lung cancer prevention and therapy. Epithelial Specific ETS-1 (ESE-1) is a transcription factor associated with several types of cancer. However, the significance of ESE-1 in human non-small cell lung cancer (NSCLC) remains unclear. The objective of this dissertation was to investigate if ESE-1 expression influences the tumorigenic and metastatic activity of human non-small cell lung cancer (NSCLC) and to explore the mechanisms associated with tumorigenesis and epithelial mesenchymal transition (EMT). Overexpression of ESE-1 repressed the anchorage-independent growth of human NSCLC cells (H1299 and H1703) and led to an increase of G1 arrest and apoptosis, additionally, to repress invasion and migration. Xenograft study indicated that ESE-1 expression inhibited the formation and development of the tumor. In terms of mechanistic studies, overexpression of ESE-1 downregulates NF-κB transcriptional activity in both H1299 and H1703 cells. The downregulation might be associated with inhibition of NF-κB-p65 phosphorylation. ESE-1 is a downstream target of TGF-β-stimulated EMT. Downregulation of ESE-1 by TGF-β is dependent on Smad2/3, but not on Smad4 and other alternative pathways, including ERK, p38 MAPK, JNK, RAS, GSK3, PI3K, NF-ĸB, CDC42, PKC, and Rock signaling. We identified two putative Smad responsive elements (SRE) in the ESE-1 promoter. After cloning internal deletion and point mutated clones lacking distal and proximal SRE, which were localized at the distal and proximal regions of the ESE-1 promoter between -1500 to -713, the double mutation responsible for ESE-1 transcriptional downregulation with TGF-β induction. Moreover, EMT downstream target Snail reciprocally interacts with ESE-1. Our findings indicate that ESE-1 serves as a tumor repressor in ESE-1-null NSCLC cells, and we propose a potential use of ESE-1 as a target of lung cancer chemoprevention.en_US
dc.language.isoenen_US
dc.titleTHE ROLE OF ESE-1 IN NON-SMALL CELL LUNG CANCER (NSCLC) CELLSen_US
dc.typeDissertationen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.contributor.departmentNutritionen_US
dc.subject.pqcontrolledCellular biologyen_US


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