Abstract
Adenocarcinoma of the breast is the most common cancer worldwide and accounts for the highest morbidity and mortality. The increasing global incidence of breast cancer emphasizes the need to understand the molecular mechanisms of breast tumorigenesis. The present study was designed to correlate changes in xenobiotic-metabolizing enzymes (XME), oxidative stress and NFkappaB signaling with histological grading and menopausal status in breast cancer patients. Sixty breast cancer patients histologically categorized as grades I, II and III, and as pre- and postmenopausal were chosen for the study. We analyzed phase I and phase II XME activities as well as the expression of the CYP isoforms CYP1A1 and CYP1B1, oxidative stress markers, and the expression of NFkappaB family members in tumor and adjacent tissues by immunohistochemical localization and Western blot analyses. The breast tumors analyzed in the present study were characterized by increased activities of xenobiotic-metabolizing enzymes and enhanced oxidative damage to lipids, proteins, and DNA associated with variations in the expression of NFkappaB family members. The magnitude of the changes was however more pronounced in premenopausal patients and in grade III breast tumors. The present study delineates the correlation between XME-mediated oxidative stress and NFkappaB signaling that leads to the development of breast cancer.
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