Effects of Environmental Estrogen on Apoptosis in Normal and Cancerous Breast Epithelial Cells

Abstract

To investigate the role of environmental estrogens in breast cancer cell apoptosis we began by utilizing the estrogen responsive MCF-7 breast cancer cell line. Widespread use of MCF-7 human breast carcinoma cells as a model system for breast cancer has lead to variations in these ceil between different laboratories. Although several reports have addressed these differences in terms of proliferation and estrogenic response, variations in sensitivity to apoptosis have not yet been described. We observed that TNF inhibited proliferation in MCF-7 cell variants from three different laboratories (designated M, L and N). MCF-7 M cells were resistant to TNF-induced apoptosis while MCF-7 L cells were moderately resistant to TNF's effect. A third variant, MCF-7 N, underwent apoptosis when exposed to TNF. Our results also suggest that differences in susceptibility to TNF-induced apoptosis among MCF-7 breast cancer cell variants may be explained by differences in TNFR expression, ceramide generation, differential expression of the Bcl-2 family of proteins and protease activation. The most sensitive MCF-7 cell variant was used to examine the effects of estrogens and environmental estrogens on TNF-induced apoptosis 17-beta- estradiol, o,p'DDT and alachlor were shown to suppress apoptosis in MCF-7N cells and increase expression of Bcl-2.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 1998
Accession Number
ADA353777

Entities

People

  • Matthew Burow

Organizations

  • Tulane University of Louisiana

Tags

DTIC Thesaurus Topics

  • Acids
  • Alcohols
  • Amides
  • Apoptosis
  • Azo Compounds
  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Culture Techniques
  • Hormones
  • Materials
  • Neoplasms
  • Proteins
  • Recombinant Dna
  • Tumor Cell Line

Fields of Study

  • Medicine

Readers

  • Breast cancer cell signaling and growth regulation.
  • Cellular and Molecular Pathways of Apoptosis.