AURORA KINASES IN SOLELY ESTROGEN-INDUCED ONCOGENESIS: RELATION TO CENTROSOME AMPLIFICATION AND CHROMOSOMAL INSTABILITY
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Issue Date
2008-06-02Author
Hontz, Adrianne Elizabeth
Publisher
University of Kansas
Format
180 pages
Type
Dissertation
Degree Level
PH.D.
Discipline
Pharmacology, Toxicology & Therapeutics
Rights
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
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Show full item recordAbstract
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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- Dissertations [4701]
- Pharmacy Dissertations and Theses [118]
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