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dc.contributor.advisorPohar, Kamal
dc.contributor.advisorJia, Hongtao
dc.creatorOrlosky, Ryan
dc.descriptionDenman Undergraduate Research Forum - 3rd Place Biological Sciencesen_US
dc.description.abstractDysregulation of the oncogene H-Ras pathway is widely found in human superficial bladder cancer, while a Rb mutation co-exists with H-Ras mutation in the majority of invasive tumors. Preliminary data on mice with bladder-specific H-Ras activation and other previous reports on in vitro cell line assays have indicated that cellular senescence, a defense response that leads to irreversible cell cycle arrest and provides a barrier for tumor progression, can be induced by H-Ras activation. Extra mutations in tumor suppressors such as Rb could contribute to the breaking of senescence and tumor progression. Investigation into senescence began with immunohistochemistry on human bladder samples for phosphoERK and Rb, which found that phosphoERK was more commonly involved with the initiation of bladder cancer while Rb was more involved with its progression. With this data, a double transgenic mouse model was created with constitutively activated H-Ras and knocked out Rb, which was hypothesized to break the senescence response. The mice were bred and euthanized, with their bladders’ senescent activity bladders analyzed using beta-galactosidase and p15. Interestingly, we found a significant correlation between the H&E/beta-galactosidase of the double transgenic and H-Ras mice as compared to the normal mice, showing that an extra mutation was not sufficient to break senescence at the age of 6-months. Additionally, p15 was not found to not be an effective senescent indicator, with no patterns seen between the three genotypes of mice. Further analysis includes assessment of our 1-year-old mice and investigation towards other tumor suppressors that may drive tumor progressionen_US
dc.description.sponsorshipPelotonia Undergraduate Fellowship Programen_US
dc.description.sponsorshipOSUCCC Solid Tumor Biology Programen_US
dc.publisherThe Ohio State Universityen_US
dc.relation.ispartofseriesThe Ohio State University. College of Biological Sciences Honors Theses; 2012en_US
dc.subjectbladder canceren_US
dc.subjecttumor suppressor Rben_US
dc.titleStudy of the H-Ras-Rb Axis in Oncogene Induced Senescenceen_US
dc.description.embargoNo embargoen_US

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