Aromatase Overexpression and Breast Cancer Development
Abstract
Estrogen can be metabolized to hydroxylated catechol estrogen, a genotoxic metabolite of 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-l0A cells, a benign breast epithelial cell line. During this funding period, we initially characterized the stable line, MCF-l0Aarom using tritiated water release assay and products isolation by thin layer chromatorgraphy. We demonstrated that MCF-l0Aarom cells expressed functional aromatase. We then conducted in vitro study for transformation using soft agar growth assay and in vivo tumorigenesis in nude mice. Our pilot studies allowed us to set up standards (growth time and colony size) for the soft agar assay. There is no palpable tumor formed in nude mice in which MCF-l0Aarom cells were inoculated. We also treated the MCF-l0Aarom cells in the culture with androstenedione, estradiol, and aromatase inhibitor letrozole. The samples were sent to Dr. Cavalieri for metabolites measurement.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2003
- Accession Number
- ADA423065
Entities
People
- Wei Yue
Organizations
- University of Virginia