HER-2 as a Progression Factor and Therapeutic Target in Breast Cancer
Abstract
We studied the effect of down-regulation of HER-2 expression by ribozyme-targeting on in vitro and in vivo proliferation of cancer cells. We found that colony formation in soft agar was dependent on HER-2 expression in MCF-7 breast cancer cells and SK-OV-3 ovarian cancer cells. The exciting and surprising observation that colony formation of MCF-7 cells is dependent on HER-2 expression demonstrates that already low levels of endogenous HER-2 expression can have a significant impact on breast cancer growth. We studied the molecular mechanisms responsible for these effects and found that heregulin (ligand for HER-3 and HER-4) mediated stimulation of colony formation depends on HER-2 expression in MCF-7 cells and that EGF (ligand for HER-1)-mediated stimulation of colony formation in SK-OV-3 cells is dependent on HER-2. This indicates that HER-2 is the rate limiting receptor in most heterodimeric HER-receptor complexes. Finally, HER-2 activation is not necessary to stimulate mitogenesis but is required to prevent the cells from undergoing apoptosis. Our most striking result is the observation that depletion of HER-2 prevents estradiol mediated stimulation of colony formation in MCF-7 breast cancer cells. This demonstrates the direct cross-talk between the two pathways and furthermore, that activation of a growth factor pathway is required for estradiol mediated stimulation of proliferation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1997
- Accession Number
- ADA328873
Entities
People
- Frank Czubayko
Organizations
- Georgetown University