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AURORA KINASES IN SOLELY ESTROGEN-INDUCED ONCOGENESIS: RELATION TO CENTROSOME AMPLIFICATION AND CHROMOSOMAL INSTABILITY
Hontz, Adrianne Elizabeth
Hontz, Adrianne Elizabeth
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Abstract
Estrogens play a crucial role in the causation and development of sporadic breast cancer, which accounts for ~ 90 - 95% of all breast cancer cases. To understand the molecular and cellular events involved in solely estrogen-induced oncogenesis, we studied the role of mitotic kinases, Aurora A and B, and the MDM2-p53wt pathway in estrogen-elicited oncogenesis, using two animal tumor models, the estrogen-induced tumors of the kidney in male Syrian hamsters, and the mammary gland in female ACI rats. Evidence is presented indicating that both Aurora kinase and MDM2 over-expression are under estrogen control in both tumor models studied. Our data further show that estrogens, interacting with the estrogen receptor α, elicit persistent Aurora A kinase over expression that may affect abnormal centrosome duplication, and together with the loss of p53wt activity by the over expression of MDM2 lead to estrogen-induced oncogenesis.
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Date
2008-06-02
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University of Kansas
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umi-ku-2589_1.pdf
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Keywords
Health sciences, Oncology, Pharmacology, Molecular biology, Breast cancer, Estrogen, Aurora kinases, Centrosome amplification, Chromosomal instability, Aneuploidy