Date of Graduation
2006
Document Type
Dissertation/Thesis
Abstract
Tumor angiogenesis is the development of vascularization from pre-existing vessels. It provides the tumors with sufficient nutrients and enables them to break the dormancy. Due to the imbalance of positive and negative angiogenic regulation, tumor blood vessels are usually leaky and chaotic which create accessible avenue for tumor metastasis. Phosphatidylinositol-3-kinases (PI3Ks) are lipid kinases that generate phospholipid second messengers and mediate signal transduction. Mutations of PI3Ks and constitutive activation of PI3K/AKT signaling have been frequently found in many human cancers. Reactive oxygen species are also important second messengers in various physiological and pathological processes, including tumor formation and metastasis and according to which many antioxidants are widely used in chemoprevention. We explored the importance of PI3K/AKT signaling in tumor angiogenesis by using siRNA against specific isoforms of PI3K and AKT kinases. We have demonstrated that p110α and AKT1 played an important role in tumor growth by inducing angiogenesis via increasing the expression HIF-1α and VEGF. We have found that ovarian cancer cells produced high levels of ROS compared to normal ovarian epithelial cells. Elevated levels of endogenous ROS contributed to tumor-induced angiogenesis. PI3K/AKT signaling was important to sustain the induction of VEGF by ROS via HIF-1α stabilization. We also found that resveratrol, a chemopreventive agent with ROS scavenging capacity, exerted its anti-tumorigenic and anti-angiogenic effects in part by affecting PI3K/AKT signaling. Collectively, this study provided a better understanding of the role of reactive oxygen species and PI3K/AKT signaling in tumor angiogenesis.
Recommended Citation
Xia, Chang, "The role of reactive oxygen species and PI3K /AKT signaling in tumor angiogenesis." (2006). Graduate Theses, Dissertations, and Problem Reports. 10055.
https://researchrepository.wvu.edu/etd/10055