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Growth Factor Signaling in Obesity Associated Breast Cancer

肥胖相关乳腺癌中的生长因子信号传导

基本信息

批准号：
10249366
负责人：
Elizabeth Wellberg
金额：
$ 31.61万
依托单位：
UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-21 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10249366
关键词：
Adipocytes Adipose tissue Adult Antiestrogen Therapy Biological Models Body Weight decreased Breast Cancer Cell Breast Cancer Prevention Breast Cancer therapy Caliber Clinical Dependence Diagnosis Environment Estradiol Estrogen Antagonists Estrogen Therapy Estrogen receptor positive Estrogens FGF1 gene FGF2 gene FGFR1 gene Fibroblast Growth Factor Fibroblast Growth Factor Receptors Follow-Up Studies Fostering Fulvestrant Genes Growth Growth Factor Hormones Hypertrophy Immune Insulin Resistance Lead Link Mammary Neoplasms Mediating Menopause Modeling Mus Nonesterified Fatty Acids Obese Mice Obesity PPAR gamma Pathway interactions Patient-derived xenograft models of breast cancer Patients Phosphorylation Postmenopause Pre-Clinical Model Process Production Prognostic Factor Property Regulation Reporting Resistance Role Sampling Signal Transduction Therapeutic Thinness Tissue Expansion Transforming Growth Factors Tumor Subtype Weight Gain Woman Xenograft Model breast cancer progression cancer cell comorbidity deprivation diet-induced obesity epidemiology study hormone therapy in vitro Model in vivo malignant breast neoplasm mortality neoplastic cell novel overexpression pre-clinical receptor response tumor tumor progression

项目摘要

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.

肥胖相关er阳性乳腺癌中的生长因子信号