Date of Graduation
School of Medicine
Microbiology, Immunology, and Cell Biology
Hypoxia inducible factor-1 is a heterodimeric basic-loop-helix transcription factor composed of two subunits, HIF-1alpha and HIF-1beta. HIF-1beta is constitutively expressed in cells, while HIF-1alpha is upregulated by hypoxia as well as growth factors and oncogenes. In this study we focus on the regulation of HIF-1alpha expression by phosphatidylinositol-3 kinase (PI3K), and novel functions of HIF-1alpha. Chapter 1 of this dissertation, consists of background and a brief review of the literature regarding PI3K signaling and HIF-1alpha. Chapter 2 focuses on the observation that basal HIF-1alpha expression is upregulated in ovarian cancer and the mechanism by which PI3K regulates this effect. Chapter 3 show the results of inhibition of HIF-1alpha using small interfering RNA (siRNA) in several in vivo models of ovarian cancer. Chapter 4 presents data showing that manipulation of HIF-1alpha expression affects cancer cell sensitivity to common chemotherapeutic agents. Chapter 5 discusses a novel target of HIF-1, cyclooxygenase-2. In chapter 6, we present the overall summary and conclusions of this dissertation.
Skinner, Heath Devin, "The regulation and role of hypoxia inducible factor-1 (HIF-1) in human cancer" (2007). Graduate Theses, Dissertations, and Problem Reports. 4335.