Aromatase Overexpression and Breast Cancer Development
Abstract
While the relevance of estrogen to established breast cancer is well documented, the role of estrogen in breast cancer initiation is still unclear. The carcinogenic effect of estrogen is mediated by its genotoxic metabolites. We hypothesized that increases in estradiol concentration in breast tissue will lead to accumulation of genotoxic metabolites and eventually causes breast cancer. To test this hypothesis, we proposed to overexpress aromatase into a benign breast epithelial cell line, MCF- 10A and to determine the production of genotoxic metabolites of estrogen and cell transformation. During the first year of funding, we successfully constructed pTRE-arom vector. Using our MCF-7Tet-off cells, we demonstrated that this vector expresses functional aromatase which is tightly controlled by tetracycline. Meanwhile, we attempted to establish MCF- lOATet-off cell line that is required for tetracycline-controlled expression of aromatase. However, MCF-lOA seems not suitable for tetracycline-controlled gene expression because it showed very high basal expression of the gene tested (luciferase reporter gene) and tetracycline does not regulate gene expression. Therefore, we used alternative approach to establish a stable line of MCF-1OA that expresses high levels of aromatase. We fulfilled the tasks scheduled for the first year of funding. The resultant MCF-lOA arom cells are ready for the future studies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA410094
Entities
People
- Jiping Wang
- Wei Yue
- Yuebai Li
Organizations
- University of Virginia