Flint, Alfred Frederick, authorHanneman, William H., advisor2024-03-132024-03-132007https://hdl.handle.net/10217/237730Human Epidermal Growth Factor 2 (HER-2, neu or erbB-2) is a protein that influences cell proliferation, morphological differentiation, and cell motility. Additionally, over expression of HER-2 has been shown to promote growth and invasion of cells of mammary neoplasia in vivo. Over expression of HER-2 has been identified in 25-30% of human and canine mammary neoplasms and osterosarcomas though the prognostic significance remains unclear. HER-2 over expression in human breast cancer correlates with a more aggressive tumor type, poor prognosis and resistance to chemotherapeutic agents. However, patients with breast cancer over-expressing HER-2 have benefited from anti-HER-2 therapy. By targeting HER-2, cell proliferation is subsequently inhibited by blocking intracellular signaling with direct targets to the cell cycle machinery. The studies presented examine the complex protein interactions of HER-2 in mammary neoplasia and osteosarcoma in canine patients. Real-time RT-PCR was used to evaluate HER-2 expression in 7 canine OSA cell lines and 10 canine OSA tissue samples. HER-2 is significantly over expressed in 86% (6/7) of the cell lines and 40% (4/10) of the OSA tissues samples. Given the importance of HER-2 in human breast cancer, the finding of HER-2 over expression in canine OSA may be important in further understanding the pathogenesis and possible therapies of OSA. Histomorphologic characterization and immunohistochemical analysis of HER-2, caveolin 1 (CAV-1), and estrogen receptor alpha (ERα) was performed on 144 canine mammary tumors from 44 different breeds. HER-2 was over expressed (score 3) in 23.4% (85/137) of the lesions. Patients with lesions over-expressing HER-2 had a 109d decrease in the median time to reoccurrence and a 276d decrease in median survival time. CAV-1 showed little or no expression in 31% (45/139) of lesions. However when CAV-1 was over expressed (score 2-3) patients had a decrease in the median time to reoccurrence of 236d and a decrease in median survival time of 292d. Finally, ERα expression in the cytoplasm was correlated to lesions that were classified as benign. The immunohistochemical evaluation of HER-2, CAV-1, and ERα support their use in prognostic evaluation.born digitaldoctoral dissertationsengCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.CAV-1canineestrogen receptor alphaHER-2mammary tumorsosteosarcomasurgeryoncologymedicineTextPer the terms of a contractual agreement, all use of this item is limited to the non-commercial use of Colorado State University and its authorized users.