Aromatase Overexpression and Breast Cancer Development
Abstract
Estrogen can be metabolized to hydroxylated catechol estrogen, a genotoxic metabolite or estrogen, which causes DNA damage and tumors in animal models. In situ synthesis of estrogen in the breast through aromatase results in high tissue estrogen concentrations. We hypothesized that overexpression of aromatase in breast tissue increases tissue estradiol concentrations and consequent genotoxic metabolites, and eventually causes breast cancer. To test our hypothesis, we stably expressed aromatase cDNA in MCF-10A cells, a benign breast epithelial cell line (MCF-10Aarom) . We demonstrated that MCF- 10arom cells expressed functional aromatase using tritiated water release assay and products isolation by thin layer chromatography. MCF-10Aarom cells, incubated for 3 months with aromatase substrate, androstenedione, formed colonies in soft agar indicating the overexpression of aromatase induces cellular transformation. MCF-10Aarom cells have all enzymes required to convert estrogen to catechoestrogens and quinine. Overexpression of aromatase enhanced production of genotoxic metabolites, which could be blocked by aromatase inhibitor, letrozole.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2005
- Accession Number
- ADA442269
Entities
People
- Eleanor Rogan
- Ercole Cavalieri
- Jiping Wang
- Richard Santen
- Sandra Gunselman
- Wei Yue
Organizations
- University of Virginia