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

Rasmus Koefoed Petersen; Signe Liv Benzon Larsen; Ditte Marie Jensen; Jane Christensen; Anja Olsen; Steffen Loft; Christine Lydia Nellemann; Kim Overvad; Karsten Kristiansen; Anne Tjønneland; Ulla Vogel

doi:10.1016/j.canlet.2011.10.009

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

Rasmus Koefoed Petersen, Signe Liv Benzon Larsen, Ditte Marie Jensen, Jane Christensen, Anja Olsen, Steffen Loft, Christine Lydia Nellemann, Kim Overvad, Karsten Kristiansen, Anne Tjønneland, Ulla Vogel

24 Citations (Scopus)

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 Pro ¹²Ala 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.

Original language	English
Journal	Cancer Letters
Volume	315
Issue number	1
Pages (from-to)	59-68
Number of pages	10
ISSN	0304-3835
DOIs	https://doi.org/10.1016/j.canlet.2011.10.009
Publication status	Published - 1 Feb 2012

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title = "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 of the wildtype Pro-allele of PPARG Pro 12Ala 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.",

author = "Petersen, {Rasmus Koefoed} and Larsen, {Signe Liv Benzon} and Jensen, {Ditte Marie} and Jane Christensen and Anja Olsen and Steffen Loft and Nellemann, {Christine Lydia} and Kim Overvad and Karsten Kristiansen and Anne Tj{\o}nneland and Ulla Vogel",

year = "2012",

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doi = "10.1016/j.canlet.2011.10.009",

language = "English",

volume = "315",

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journal = "Cancer Letters",

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TY - JOUR

T1 - PPARgamma-PGC-1alpha activity is determinant of alcohol related breast cancer

AU - Petersen, Rasmus Koefoed

AU - Larsen, Signe Liv Benzon

AU - Jensen, Ditte Marie

AU - Christensen, Jane

AU - Olsen, Anja

AU - Loft, Steffen

AU - Nellemann, Christine Lydia

AU - Overvad, Kim

AU - Kristiansen, Karsten

AU - Tjønneland, Anne

AU - Vogel, Ulla

PY - 2012/2/1

Y1 - 2012/2/1

N2 - 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 Pro 12Ala 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.

AB - 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 Pro 12Ala 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.

U2 - 10.1016/j.canlet.2011.10.009

DO - 10.1016/j.canlet.2011.10.009

M3 - Journal article

C2 - 22050908

SN - 0304-3835

VL - 315

SP - 59

EP - 68

JO - Cancer Letters

JF - Cancer Letters

IS - 1

ER -

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

Abstract

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