Apoptosis and Tumor Invasion in Breast Cancer
Abstract
We have created a series of breast cancer cell lines, transfected with green fluorescent protein (GFP) that can be use to examine the effects of anti-estrogens on the invasive potential of breast cancer cells that survive anti-estrogen therapy. We have tested 20 of these cell lines to establish that they have retained their sensitivity to tumor necrosis factor-alpha (TNFalpha) and to several anti-estrogens (tamoxifen, 4-hydroxytamoxifen and ZM 182,780). Most, but not all of the cell lines induce apoptosis after treatment with anti-estrogens. After 72 h of treatment 60-70% of the transfected cells die by apoptosis, while 40% of the cells survive. During the apoptotic process the cells induce the transcription of several extracellular matrix proteases (particularly cathepsin B and MMP-9) and down regulate the expression of at least one matrix metalloprotease inhibitor (TiMP-1). These data provide support for our hypothesis that while anti-estrogen therapy induces cell death in the majoroty of hormone responsive cells, a same population of cells may survive the treatment but may induce the enzymes required for invasion. If further experimentation demonstrates directly that there is an increase in the invasive potential of the surviving cells it will suggest anti-estrogen therapy for early stage disease or as a chemo-preventive strategy is contra-indicated.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1998
- Accession Number
- ADB248365
Entities
People
- Martin Tenniswood
Organizations
- The W. Alton Jones Cell Science Center