Date on Master's Thesis/Doctoral Dissertation

5-2012

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Physiology and Biophysics

Committee Chair

Kakar, Sham Sunder

Author's Keywords

Ovarian cancer; Transgenic mice; PTTG; Treatment strategies; Doxorubicin; Withaferin A

Subject

Ovaries--Cancer--Treatment

Abstract

This dissertation is a hypothesis-driven research oriented study to determine the role of the pituitary-tumor transforming gene (PTTG) in ovarian cancer, specifically if it is involved in neoplastic transformation leading to tumorigenesis through oncogene activation and the involvement of tumor-suppressor gene, p53. Furthermore, generation of a useful ovarian cancer mouse model provides a platform technology to screen for ovarian cancer diagnosis and treatment options. This dissertation is divided into four chapters covering the etiology of ovarian cancer and a novel treatment strategy for ovarian cancer. The first chapter reviews the related literature encompassing the etiology of ovarian cancer, mouse models of ovarian cancer, the biological function of PTTG, the role of PTTG in cancer and diabetes, and mouse models using PTTG as a transgene. The second chapter studies the role of PTTG in tumorigenesis in vivo through the generation ofa PTTG transgenic (TgPTTG) mouse model observed at various ages, ranging from 4 to 10 months. The third chapter is a preliminary study investigating the signaling mechanisms affected by chemotherapy agent doxorubicin in combination with withaferin A in vitro and in vivo for the treatment of ovarian cancer. The fourth chapter is a discussion of the utility of ovarian cancer mouse models and the consequences of the lack of a working model.

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