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

Elise A. Triano, Leslie B. Slusher, Trudy A. Atkins, John T. Beneski, Shelley A. Gestl, Reza Zolfaghari, Rathnagiri Polavarapu, Elizabeth Frauenhoffer, Judith Weisz

Research output: Contribution to journalArticle

54 Citations (Scopus)

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 ahrogation 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.

Original languageEnglish (US)
Pages (from-to)3092-3100
Number of pages9
JournalCancer Research
Volume63
Issue number12
StatePublished - Jun 15 2003

Fingerprint

Alcohol Dehydrogenase
Human Mammary Glands
Carcinogenesis
Breast
Breast Neoplasms
Ethanol
Epithelium
Micronutrients
Retinoids
Tretinoin
Vitamin A
Alcohol Drinking
NAD
DNA Damage
Reverse Transcription
Immunohistochemistry
RNA
Polymerase Chain Reaction
Messenger RNA
Enzymes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Triano, Elise A. ; Slusher, Leslie B. ; Atkins, Trudy A. ; Beneski, John T. ; Gestl, Shelley A. ; Zolfaghari, Reza ; Polavarapu, Rathnagiri ; Frauenhoffer, Elizabeth ; Weisz, Judith. / Class I alcohol dehydrogenase is highly expressed in normal human mammary epithelium but not in invasive breast cancer : Implications for breast carcinogenesis. In: Cancer Research. 2003 ; Vol. 63, No. 12. pp. 3092-3100.
@article{f1494c1f8f044347b65f2f22f818173b,
title = "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 ahrogation 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.",
author = "Triano, {Elise A.} and Slusher, {Leslie B.} and Atkins, {Trudy A.} and Beneski, {John T.} and Gestl, {Shelley A.} and Reza Zolfaghari and Rathnagiri Polavarapu and Elizabeth Frauenhoffer and Judith Weisz",
year = "2003",
month = "6",
day = "15",
language = "English (US)",
volume = "63",
pages = "3092--3100",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "12",

}

Class I alcohol dehydrogenase is highly expressed in normal human mammary epithelium but not in invasive breast cancer : Implications for breast carcinogenesis. / Triano, Elise A.; Slusher, Leslie B.; Atkins, Trudy A.; Beneski, John T.; Gestl, Shelley A.; Zolfaghari, Reza; Polavarapu, Rathnagiri; Frauenhoffer, Elizabeth; Weisz, Judith.

In: Cancer Research, Vol. 63, No. 12, 15.06.2003, p. 3092-3100.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Class I alcohol dehydrogenase is highly expressed in normal human mammary epithelium but not in invasive breast cancer

T2 - Implications for breast carcinogenesis

AU - Triano, Elise A.

AU - Slusher, Leslie B.

AU - Atkins, Trudy A.

AU - Beneski, John T.

AU - Gestl, Shelley A.

AU - Zolfaghari, Reza

AU - Polavarapu, Rathnagiri

AU - Frauenhoffer, Elizabeth

AU - Weisz, Judith

PY - 2003/6/15

Y1 - 2003/6/15

N2 - 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 ahrogation 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.

AB - 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 ahrogation 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.

UR - http://www.scopus.com/inward/record.url?scp=0038069373&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038069373&partnerID=8YFLogxK

M3 - Article

C2 - 12810634

AN - SCOPUS:0038069373

VL - 63

SP - 3092

EP - 3100

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 12

ER -