Role of Molybdenum Hydroxylase Generated Free Radicals in Alcohol Induced Breast Cancer

摘要

Alcohol consumption by women is an important risk factor for breast cancer (BC) found to promote BC through reactive oxygen species (ROS) induced carcinogenesis. Our experiments revealed that alcohol dehydrogenase (ADH), aldehyde oxidase (AOX), and xanthine oxidoreductase (XOR) are expressed and regulated in breast tissues. Mammary gland XOR and AOX were efficient sources of ROS using the products of alcohol breakdown. The human gene for XOR was activated in mammary glands and mammary epithelial cells by cytokines and hormones known to mediate mammary gland development, and activation was accompanied ROS generation. XOR was found to be an inducible source of ROS in mammary epithelial cells. Conversion of XOR from D-form to 0-form is necessary for the formation of ROS by XOR, and we discovered an important structural determinant of the conversion. The human AOX gene was also expressed in mammary epithelial cells and its gene was activated by transcription factors known promote alcohol metabolism.