Effects of Environmental Estrogens on Apoptosis in Normal and Cancerous Breast Epithelial Cells
Abstract
Estrogens and environmental estrogens were shown to suppress apoptosis in MCF-7 cells and increase expression of Bcl- 2. These same compounds were unable to suppress apoptosis of MDA-MB-231 cells suggesting an ER-dependent mechanism of action. Phytoestrogens represent another category of environmental estrogens some of which our results demonstrate possess anti-estrogenic activity and induce apoptosis in MCF-7 cells. To investigate the role of Bcl-2 in TNF resistance by estrogens a Bcl-2 expression vector was transfected into MCF-7 cells and stable clones were established. These clones express higher levels of Bcl-2 as compared to vector transfected MCF-7N/Neo cells. The BCL-2 overexpressing cells exhibited a greater resistance to apoptosis as compared to MCF-7N/Neo cells. However suppression of ER function by the anti-estrogen 101182,780 blocked the ability of Bcl-2 to inhibit apoptosis suggesting that Bcl-2 was necessary but not sufficient for suppression of apoptosis by estrogen signaling. Subsequent experiments provided evidence that ER suppression of apoptosis was dependent upon both Bcl-2 expression and regulation of signaling by the mitogen-activated protein kinase cascades. We have identified environmental compounds that function to regulate the apoptotic response of breast carcinoma cells through regulation of MAPK signaling and Bcl-2 expression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2001
- Accession Number
- ADA406230
Entities
People
- Matthew E. Burow
Organizations
- Tulane University of Louisiana