Obesity and Postmenopausal Breast Cancer Risk: Determining the Role of Growth Factor-Induced Aromatase Expression
Abstract
In postmenopausal women, obesity is associated with a worse breast cancer prognosis, and this may be related to these patients reduced response rate to aromatase inhibitor treatment. Obesity is accompanied by elevated levels of growth factors and inflammatory cytokines that can promote tumorigenesis and regulate the expression and activity of aromatase, the key enzyme in the synthesis of estrogen from androgens. The purpose of this project is to elucidate the role of local aromatase expression and activity in the promotion of breast cancer progression in obese postmenopausal women. Results have demonstrated that serum from obese postmenopausal women stimulates greater aromatase expression in adipose stromal cells (ASC) and MCF-7 breast cancer cells via direct and indirect mechanisms in comparison to serum from normal weight subjects. The obesity-induced aromatase expression in ASC and MCF-7 cells is associated with elevated breast cancer cell estrogen receptor alpha activity in the presence of exogenous testosterone. Further data indicates that the indirect effects of the obese sera on ASC aromatase expression are primarily mediated by inflammatory cytokine-induced prostaglandin E2 production by the cancer cells and macrophages. Based on these findings, future animal and human studies investigating the efficacy of an aromatase inhibitor/COX-2 inhibitor combination treatment in the obese postmenopausal population are being developed.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2014
- Accession Number
- ADA596733
Entities
People
- Laura Bowers
Organizations
- University of Texas at Austin