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Title: Investigations on Rac1b Under Normoxia and Hypoxia
Authors: Chu, Vincent
Advisors: Nelson, Celeste M.
Department: Chemistry
Class Year: 2015
Abstract: The overexpression of Rac1b, a constitutively active Rho GTPase, has been linked to human breast cancer, among other cancers, and has been shown to promote epithelial-mesenchymal transition (EMT) in culture when it is localized at the cell membrane. It has been suggested that hypoxia, a common condition in tumor cores, decreases Rac1b localization to the membrane. This thesis reexamines the effect of hypoxia on Rac1b localization and proposes two mechanisms by which hypoxia may decrease membrane localization of Rac1b. The first hypothesis is that hypoxia decreases the amount of lipid rafts in the cell membrane, which have been shown to be required for membrane localization of Rac1b. No difference in membrane order was detected using the di-4-ANEPPDHQ dye, suggesting that this mechanism does not explain Rac1b translocation under hypoxia. Second, the hypothesis that hypoxia inhibits Rac1b prenylation was examined using western blotting. Although the prenylation state of Rac1b was not resolvable with the western blot conditions tried, other techniques may be used in the future to test this hypothesis. Aside from studying Rac1b localization under hypoxia, this thesis also attempted to determine the effect of Rac1b on the phosphorylation of YAP, a key transcription factor in the Hippo signaling pathway that activates the transcription of genes related to cell survival and proliferation. Western blotting and immunofluorescent staining for phosphorylated YAP were inconclusive, and the experiments need to be refined to show whether Rac1b overexpression affects YAP phosphorylation. Further research to gain insight on Rac1b function will increase understanding of the processes that underlie cancer development and possibly provide new avenues for cancer treatment.
Extent: 50 pages
Type of Material: Princeton University Senior Theses
Language: en_US
Appears in Collections:Chemistry, 1926-2016

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