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Browsing by Author "Flint, Alfred Frederick, author"

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    Protein expression of HER-2, CAV-1 and ER alpha in canine mammary tumors and canine osteosarcoma
    (Colorado State University. Libraries, 2007) Flint, Alfred Frederick, author; Hanneman, William H., advisor
    Human 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.