# Growth Factor Signaling in Obesity Associated Breast Cancer

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2021 · $316,131

## Abstract

Growth Factor Signaling in Obesity-Associated ER-positive Breast Cancer
 Obesity is a negative prognostic factor for women with breast cancer. The estrogen receptor
positive (ER+) subtype is the most commonly diagnosed, representing ~70% of cases. Epidemiological
studies have implicated adult weight gain, characterized by adipose tissue expansion, as one
underlying driver of the obesity-breast cancer relationship. Overall, a barrier to our understanding about
what drives breast cancer progression in women with obesity is the lack of preclinical models that
combine obesity and its comorbidities, the postmenopausal environment, and ER+ tumors. I have
created a diet-induced obesity/xenograft (DIOX) model to study breast cancer progression and
response to therapy. Weight gain and adipocyte diameter were positively associated with adipose
production of fibroblast growth factor (FGF1), tumor cell activation of FGFR1, and estrogen-
independent growth of ER+ breast tumors. Our overarching hypothesis that expanding adipose
tissue (weight gain) promotes cancer progression through adipocyte FGF production and
FGFR/ER crosstalk in breast cancer cells. We will use in vivo and in vitro models to investigate the
regulation of FGF1 production by adipose tissue and the resulting crosstalk between tumor FGFR1 and
ER in the following specific aims: 1) Determine whether free fatty acids (FFAs) induce PPARγ -
mediated FGF1 expression in hypertrophic adipocytes. 2) Determine whether estrogen-
independent growth of FGFR1 overexpressing tumors depends on signaling through ER.
Overall, the proposal will investigate the contribution of factors extrinsic (host adipose tissue FGF1;
Aim1) and intrinsic (tumor FGFR1/ER crosstalk; Aim2) to the tumor that may drive obesity-associated
breast cancer progression using novel preclinical and in vitro model systems.

## Key facts

- **NIH application ID:** 10249366
- **Project number:** 5R01CA241156-03
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Elizabeth Wellberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $316,131
- **Award type:** 5
- **Project period:** 2020-07-21 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249366

## Citation

> US National Institutes of Health, RePORTER application 10249366, Growth Factor Signaling in Obesity Associated Breast Cancer (5R01CA241156-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10249366. Licensed CC0.

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