Alcohol intake stimulates epithelial proliferation in an authentic model of the human breast

•The mammary glands of pigs can be used to model alcohol effects on the breast.•Alcohol intake stimulates epithelial proliferation in the mammary gland.•Alcohol intake promotes histomorphogenic changes and STAT5 phosphorylation. The voluntary consumption of alcohol by humans is a modifiable lifestyl...

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Published in:Reproductive toxicology (Elmsford, N.Y.) Vol. 54; pp. 93 - 100
Main Authors: Schennink, Anke, Trott, Josephine F., Berryhill, Grace E., Donovan, Caitlin E., Manjarin, Rodrigo, VanKlompenberg, Monica K., Rowson-Hodel, Ashley R., Luis, Michelle-Yvette Osorio, Hovey, Russell C.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01.07.2015
Subjects:
Age Factors
Alcohol
Alcohol Drinking - adverse effects
Animals
Breast Neoplasms - chemically induced
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Proliferation - drug effects
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Epithelial Cells - pathology
Ethanol - blood
Ethanol - toxicity
Female
Humans
Mammary gland
Mammary Glands, Animal - drug effects
Mammary Glands, Animal - growth & development
Mammary Glands, Animal - metabolism
Mammary Glands, Animal - pathology
Models, Animal
Phosphorylation
Risk Assessment
Risk Factors
Sexual Development
STAT5 Transcription Factor - metabolism
Swine
Terminal ductal lobular unit
P-Stat5
IGF-I
PR
DAB
BAC
IGFBP3
Alcohol
PH3
MG
Mammary gland
Terminal ductal lobular unit
TDLU
ISSN:0890-6238, 1873-1708, 1873-1708
Online Access:Get full text
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Summary:•The mammary glands of pigs can be used to model alcohol effects on the breast.•Alcohol intake stimulates epithelial proliferation in the mammary gland.•Alcohol intake promotes histomorphogenic changes and STAT5 phosphorylation. The voluntary consumption of alcohol by humans is a modifiable lifestyle factor that has been consistently linked to a woman's risk of developing breast cancer. We have used an animal model that closely recapitulates breast development in humans to study the effect of alcohol intake on breast growth and morphology. Pubertal female pigs were fed alcohol for 4–5 weeks at 19–21% of total caloric intake, which led to average blood alcohol concentrations of 115–130mg/dL. Alongside increased liver mass, alcohol intake promoted the formation of distended ductules within lobular units in association with increased epithelial proliferation. Alcohol consumption also increased phosphorylation of the transcription factor STAT5 in the mammary epithelium, but did not lead to any evidence of precocious lactogenesis. In conclusion, feeding alcohol to female pigs having a similar physiology and mammary gland morphology to humans during a reproductive state equivalent to human adolescence leads to increased mammary gland proliferation and development of atypical lobular structures. These changes may phenocopy how alcohol intake increases the risk for developing breast cancer in humans.
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ISSN:0890-6238
1873-1708
1873-1708
DOI:10.1016/j.reprotox.2014.10.020