PPARgamma-PGC-1alpha activity is determinant of alcohol related breast cancer

Abstract Alcohol is a risk factor for postmenopausal breast cancer. One of several proposed mechanisms is that alcohol-related breast cancer is caused by increased sex hormone levels. PPARγ inhibits aromatase transcription in breast adipocytes. We reproduced previously found allele-specific effects...

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Bibliographic Details
Published in:Cancer letters 2012-02, Vol.315 (1), p.59-68
Main Authors: Petersen, Rasmus Koefoed, Larsen, Signe Benzon, Jensen, Ditte Marie, Christensen, Jane, Olsen, Anja, Loft, Steffen, Nellemann, Christine, Overvad, Kim, Kristiansen, Karsten, Tjønneland, Anne, Vogel, Ulla
Format: Article
Language:English
Subjects:
adipocytes
Aged
Alcohol
Alcohol Drinking - adverse effects
Alcohol Drinking - epidemiology
Alcohol Drinking - metabolism
Breast cancer
breast neoplasms
Breast Neoplasms - epidemiology
Breast Neoplasms - metabolism
Denmark - epidemiology
ethanol
Ethanol - poisoning
Female
Genes
Heat-Shock Proteins - antagonists & inhibitors
Heat-Shock Proteins - metabolism
Hematology, Oncology and Palliative Medicine
Hormone replacement therapy
Humans
Menopause
Middle Aged
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Polymorphism
Population-based
postmenopause
PPAR gamma - antagonists & inhibitors
PPAR gamma - metabolism
PPARgamma
risk factors
Transcription Factors - antagonists & inhibitors
Transcription Factors - metabolism
transcriptional activation
unspecific monooxygenase
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Summary:Abstract Alcohol is a risk factor for postmenopausal breast cancer. One of several proposed mechanisms is that alcohol-related breast cancer is caused by increased sex hormone levels. PPARγ inhibits aromatase transcription in breast adipocytes. We reproduced previously found allele-specific effects of the wildtype Pro-allele of PPARG Pro12 Ala in alcohol related breast cancer. In transiently transfected cells, transcriptional activation by PPARγ and the PPARγ-PGC-1α complex was inhibited by ethanol. PPARγ 12Ala-mediated transcription activation was not enhanced by PGC-1α, resulting in allele-specific transcription activation by the PPARγ 12Pro-PGC-1α complex. Our results suggest that PPARγ and PGC-1α activity is an important determinant of alcohol related breast cancer.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2011.10.009