The study of the genomic polymorphism and expression of manganese-containing superoxide dismutase in patients with breast cancer in Taiwanese women

Autor: Bao-Wen Hu, 胡寶文
Rok vydání: 2006
Druh dokumentu: 學位論文 ; thesis
Popis: 94
Breast cancer is the most common cancer worldwide, accounts for the highest morbidity and mortality. Breast cancer has become one of ten major female cancers in Taiwan. The increasing incidence of breast cancer emphasizes the need to understand the various mechanisms involved in breast tumorgenesis. The etiology of breast cancer is multifactorial. Damage to breast epithelium by reactive oxygen species (ROS) is important in the initiation and promotion of cells to neoplastic growth. Oxidative stress plays an important role in breast carcinogenesis. The most important cellular protective mechanisms against oxidative stress are antioxidant enzymes. Superoxide dimutases (SODs) decompose superoxide radicals to hydrogen peroxide and then consumed by multiple enzymes such as catalase and glutathione peroxidase. Within mitochondria manganese superoxide dismutase (Mn SOD) provides a major defense against oxidative damage by ROS. We analyzed the MnSOD genomic polymorphism and evaluated the relationships of the MnSOD genotype and protein expression. After analysis, we found that patients who were Ala carrier genotype had a higher frequency of the negative expression of HER2 (human epidermal growth factor receptor-2) protein. We suggested that there were the relationships between MnSOD genomic polymorphism and prognosis of breast cancer. To clarify the roles of MnSOD in malignancy, we investigated the expression of MnSOD genotype and protein expression between tumor and adjacent tumor-free tissue. We found that there was significantly stronger MnSOD expression in adjacent tumor-free tissue than in tumor tissue. According to the result, we suggested that MnSOD might act as a tumor suppressor gene in the cases. In addition, there were also significantly stronger MnSOD expression and more MnSOD positive cases in the IDC than in the DCIS by immunohistochemical staining (IHC). We thought that the strong expression of MnSOD in adjacent cancer-free epithelium cells was in order to protect cells from damage induced by free radicals. The expression of MnSOD was decreased in DCIS because MnSOD were consumed by the growth of free radicals. However, the expression of MnSOD was increased in IDC for the purpose of tumor cells to infringe on adjuvant epithelium cells.
Databáze: Networked Digital Library of Theses & Dissertations