HER-2 as a Progression Factor and Therapeutic Target in Breast Cancer.
Abstract
In the past cycle under this award, we analyzed the interaction of estrogen and HER-2 with respect to MCF-7 human breast cancer cell growth (goal 2). We had observed previously that upon reduction of llER-2 in MCF-7 cells by ribozyme-targeting estradiol lost its ability to induce anchorage- independent colony formation in soft agar of the tumor cell% as well as promote cell growth on dish surfaces. We now show data and report that this is due to the failure of estradiol to inhibit apoptosis when HER-2 is reduced in MCF-7 cells. In contrast, no change in the progression through into the cell cycle after estradiol was observed. By cDNA array analysis we traced this effect of the HER-2 reduction to a series of genes involved in the regulation of apoptosis. Expression of genes regulating apoptosis was affected significantly when the estrogen effect on cell growth was blocked by the reduction of HER-2. In contrast, the expression of genes regulating the cell cycle did not appear to be affected to a measurable extent. Further analysis of individual genes involved in this cross-talk between estro%en and HER-2 signal transduction is ongoing.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1999
- Accession Number
- ADA372251
Entities
Organizations
- Georgetown University