Diet, Estrogen, and Breast Cancer

Project: Research project

Project Details

Description

We hypothesize that, compared to AE mice on an unrestricted high
fat diet (ad lib HFD), AE mice on a time-restricted high fat diet (tRF-HFD) will show (1)
normalized weight, (2) lower aromatase activity in breast adipose tissue, (3) reduced local
estrogen in the breast, and (4) a lower predisposition to developing breast cancer via the
AMPK pathway. Mechanistically, we propose that tRF-HFD-induced weight loss triggers
AMPK signaling pathways that downregulate aromatase expression via the proximal
promoter II/I.3 in breast adipose tissue, thereby decreasing estrogen production and
preventing breast cancer development.

Our long-term goal is to determine the mechanism
responsible for the link between obesity and increased risk of developing postmenopausal
breast cancer. Specifically, we propose that tRF-HFD-induced weight loss triggers
AMPK signaling pathways that decrease aromatase expression via a robust
downregulation of its proximal promoter II/I.3 region in breast adipose tissue. The two
objectives of this proposal are: (1) to assess the effect of tRF-HFD or ad lib HFD on
aromatase expression via promoter PII/I.3 and estrogen production; and (2) to determine
the effect of tRF-HFD or ad lib HFD on mammary carcinogenesis. As a future aim, we
plan to define the molecular mechanisms underlying tRF-HFD regulation of the
AMPK/aromatase pathway and estrogen formation in mammary tissue.
Aim 1: To assess the effect of tRF-HFD or ad lib HFD on aromatase expression via
promoter PII/I.3 and estrogen production.
Aim 2: To determine the effect of tRF-HFD or ad lib HFD on breast carcinogenesis.
StatusFinished
Effective start/end date9/1/138/31/15

Funding

  • Northwestern Memorial Hospital (Master Agmt/9-22-13/EX-B20)

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