Mitochondrial Structure and Reactive Oxygen Species in Mammary Oncogenesis

摘要

Oxidative stress may play a role in human oncogenesis, including breast cancer. The mitochondria are most common sources of reactive oxygen species (ROS) responsible for most oxidative stress. This project evaluates the role of mitochondrial abnormalities in oxidative stress in breast cancer development. Complex II mutant subunits, affecting the quinone-binding site or the heme b ligand binding site, were generated and analyzed in both cell culture and transgenic mouse systems in terms of mitochondrial functions, ROS production and oncogenesis. Results from this study demonstrate that short-term expression of these mutants induces apoptosis in the cells; and transgenic mice harboring these mutant complex II subunits develop tissue vascularization and tumors at advanced ages. These findings suggest a role of oxidative stress in breast cancer development and progression, and provide clues on whether antioxidants are beneficial in prevention and treatment of such important cancer in women.