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Impact of Obesity on Mammary Gland Inflammation and Local Estrogen Production

Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Obesity rates have risen dramatically over the past century, having nearly doubled since 1980. Changes in diet and lifestyle have contributed to this occurrence in younger women, and changing hormone levels during the menopausal transition has no doubt exacerbated the issue in older women. The relationship between adiposity and breast cancer is clear in postmenopausal women, and is intimately linked to the increased expression of aromatase and the production of estrogens within the breast adipose. This, in turn, is highly dependent on the localized chronic inflammation observed in obese adipose. This review will therefore explore the relationship between obesity, inflammation and estrogens, with a particular focus on the molecular regulation of aromatase in the postmenopausal breast in the context of obesity and breast cancer.

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Fig. 1

Abbreviations

AMPK:

AMP-activated protein kinase

AP-1:

Activating protein-1

ATF2:

Activating transcription factor 2

CLS:

Crown-like structures

COX-2:

Cyclooxygenase-2

CRE:

cAMP response element

CREB:

cAMP response element binding protein

CRTC:

CREB-regulated transcription coactivator

E2:

Estradiol-17β

Egr:

Early growth response

EP:

E-prostanoid

GR:

Glucocorticoid receptor

HIF1α:

Hypoxia inducible factor 1α

IL-1β:

Interleukin-1β

IL-6:

Interleukin-6

JNK:

C-jun NH2-terminal kinase

LKB1:

Liver kinase B1

LRH-1:

Liver receptor homolog-1

MAPK:

P38 mitogen-activated protein kinase

NF-κB:

Nuclear factor κB

PGE2 :

Prostaglandin E2

PKA:

Protein kinase A

PKC:

Protein kinase C

TNFα:

Tumor necrosis factor α

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Acknowledgments

This work was supported by NHMRC (Australia) Project Grant # GNT1005735 and by a grant from the National Breast Cancer Foundation (NC-14-011), and by the Victorian Government Operational Infrastructure Support Program. KAB is supported by an NHMRC (Australia) Career Development Award GNT1007714.

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Brown, K.A. Impact of Obesity on Mammary Gland Inflammation and Local Estrogen Production. J Mammary Gland Biol Neoplasia 19, 183–189 (2014). https://doi.org/10.1007/s10911-014-9321-0

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