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Title: Oxygen Tension and Rac1b Localization
Authors: Halpern, Samantha Brooke
Advisors: Nelson, Celeste M.
Department: Chemical and Biological Engineering
Class Year: 2014
Abstract: Rac1b, a splice variant of the Rac1 small GTPase, has been implicated in the progression of many human cancers, including breast cancer. Rac1b expression is highly localized within the cell and previous studies have reported that Rac1b must be present on the cell membrane in order to associate with its downstream effectors and to promote cancer. Hypoxia, a condition under which cells are deprived of oxygen, is a common feature of breast tumors due to impaired vascular function and decreased blood flow to the tumor core. Hypoxia has important implications in cancer in that it helps to select for more invasive tumor cells and frequently leads to cancer drug resistance. Both hypoxia and Rac1b have been implicated in the epithelial-­‐mesenchymal transition (EMT), a phenotypic change that enables cancer cells to metastasize. Given the important roles played by both hypoxia and Rac1b in the onset of EMT and promotion of cancer, this study sought to identify the effect of hypoxia on Rac1b localization. We hypothesized that hypoxia would promote the association of Rac1b with the membrane, as this would lead to the activation of downstream effectors important for cancer. We tested this by transfecting cells with a YFP-­‐Rac1b plasmid and placing the cells into a hypoxic chamber in order to visualize the effects of hypoxia on Rac1b localization. Contrary to our initial hypothesis, hypoxia actually led to the localization of Rac1b in the nucleus, instead of on the membrane. Our data show that hypoxia actually inhibits Rac1b from reaching the membrane, which demonstrates that the mechanism is much more complicated than we initially thought. If we are able to uncover this mechanism, it will have important implications for better understanding cancer progression and developing targeted cancer therapies.
Extent: 55 pages
Type of Material: Princeton University Senior Theses
Language: en_US
Appears in Collections:Chemical and Biological Engineering, 1931-2016

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