This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Triano, E. A. Articles by Weisz, J. Search for Related Content PubMed PubMed Citation Articles by Triano, E. A. Articles by Weisz, J.

Class I Alcohol Dehydrogenase Is Highly Expressed in Normal Human Mammary Epithelium but not in Invasive Breast Cancer

Implications for Breast Carcinogenesis¹

Department of Biology, West Chester University, West Chester, Pennsylvania 19383 [E. A. T., L. B. S., T. A. A., J. T. B.]; Departments of Obstetrics and Gynecology [S. A. G., J. W.], Pharmacology [R. P.], and Pathology [E. F.], Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033; and Department of Nutrition, Pennsylvania State University, University Park, Pennsylvania 16802 [R. Z.]

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.

This article has been cited by other articles:

				G. C. Barnett, M. Shah, K. Redman, D. F. Easton, B. A.J. Ponder, and P. D. P. Pharoah Risk Factors for the Incidence of Breast Cancer: Do They Affect Survival From the Disease? J. Clin. Oncol., July 10, 2008; 26(20): 3310 - 3316. [Abstract] [Full Text] [PDF]

				M. Zaitseva, B. J. Vollenhoven, and P. A.W. Rogers Retinoic acid pathway genes show significantly altered expression in uterine fibroids when compared with normal myometrium Mol. Hum. Reprod., August 1, 2007; 13(8): 577 - 585. [Abstract] [Full Text] [PDF]

				M. B. Terry, M. D. Gammon, F. F. Zhang, J. A. Knight, Q. Wang, J. A. Britton, S. L. Teitelbaum, A. I. Neugut, and R. M. Santella ADH3 genotype, alcohol intake and breast cancer risk Carcinogenesis, April 1, 2006; 27(4): 840 - 847. [Abstract] [Full Text] [PDF]

				E. F. Farias, D. E. Ong, N. B. Ghyselinck, S. Nakajo, Y. S. Kuppumbatti, and R. Mira y Lopez Cellular Retinol-Binding Protein I, a Regulator of Breast Epithelial Retinoic Acid Receptor Activity, Cell Differentiation, and Tumorigenicity J Natl Cancer Inst, January 5, 2005; 97(1): 21 - 29. [Abstract] [Full Text] [PDF]