Detoxification of
ethanol can contribute to oxidative cellular and DNA damage and, thereby, to
carcinogenesis. The potential relevance of this to breast
carcinogenesis is suggested by evidence that alcohol consumption is a risk factor for
breast cancer. It is, however, not known whether
ethanol can be metabolized in breast parenchyma. The goal of this study was to determine whether class I and/or IV
alcohol dehydrogenase (ADH), medium chain ADHs that can catalyze oxidation of
ethanol, are expressed in human breast parenchyma. Normal and neoplastic human breast tissue specimens were examined for class I and IV ADH
mRNA by reverse transcription-PCR, for
protein by immunocytochemistry and Western analysis, and for their potential to catalyze
NAD(+)-dependent oxidation of
ethanol. Together, the findings provide evidence that: (a) class I ADH is the medium-chain ADH that is expressed in human breast parenchyma, specifically in the mammary epithelium; (b) human breast parenchyma can support ADH-mediated oxidation of
ethanol; and (c) the expression of class I ADH is dramatically reduced or abrogated in invasive breast
cancers. Expression of class I ADH in normal human breast parenchyma was confirmed by probing a multiple human tissue polyA(+)
RNA. The unexpected finding of virtual abrogation of expression of class I ADH in invasive
breast cancer suggests that the
enzyme has some "
tumor suppressor" function in the mammary epithelium. The one property of class I ADH fitting this designation is its potential to catalyze the oxidation of the
micronutrient/prohormone
retinol to
retinal, the first step in the biosynthesis of
retinoic acid, the principal known mediator of the actions of
retinoids important for maintaining epithelia in a differentiated state.