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Class I alcohol dehydrogenase is highly expressed in normal human mammary epithelium but not in invasive breast cancer: implications for breast carcinogenesis.

Abstract
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.
AuthorsElise A Triano, Leslie B Slusher, Trudy A Atkins, John T Beneski, Shelley A Gestl, Reza Zolfaghari, Rathnagiri Polavarapu, Elizabeth Frauenhoffer, Judith Weisz
JournalCancer research (Cancer Res) Vol. 63 Issue 12 Pg. 3092-100 (Jun 15 2003) ISSN: 0008-5472 [Print] United States
PMID12810634 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Chlorides
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • NAD
  • Vitamin A
  • Ethanol
  • Alcohol Dehydrogenase
  • alcohol dehydrogenase IV
Topics
  • Adolescent
  • Adult
  • Alcohol Dehydrogenase (biosynthesis, genetics, physiology)
  • Breast (enzymology)
  • Breast Neoplasms (enzymology, etiology, pathology)
  • Carcinoma, Ductal, Breast (enzymology, pathology)
  • Cell Differentiation
  • Cell Transformation, Neoplastic
  • Chlorides (physiology)
  • Enzyme Induction
  • Epithelial Cells (enzymology)
  • Ethanol (metabolism)
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Middle Aged
  • NAD (metabolism)
  • Neoplasm Invasiveness
  • Neoplasm Proteins (biosynthesis, genetics, physiology)
  • Postmenopause
  • Pregnancy
  • Pregnancy Complications, Neoplastic (enzymology)
  • RNA, Messenger (analysis, biosynthesis, genetics)
  • RNA, Neoplasm (analysis, biosynthesis, genetics)
  • Vitamin A (metabolism)

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