HER-2 as a Progression Factor and Therapeutic Target in Breast Cancer
Abstract
Our studies were aimed at elucidating the contribution of HER-2 to breast cancer growth and progression to hormone independence as well as the development of resistance to treatment with cytotoxic drugs and anti-hormones. As a major tool we have used gene expression of a HER-2 truncated form and gene-specific targeting of HER-2 with hammerhead- ribozyme expression constructs. We found that expression of HER-2 is rate limiting for growth that relies on ligands for the HER-l / -3/ -4 family (EGF, heregulin. We also found that estrogen needs HER-2 for its estrogen-receptor-mediated activity in cell culture and for tumor growth in animals. The estrogenic pathway affected is the rescue from apoptosis and does not involve cell cycle effects. We also found that doxorubicin sensitivity is dependent on the presence of intact HER-2 in breast cancer cells and discovered that a truncated HER-2 splice variant acts as an endogenous inhibitor of tumor cell growth. Thus, we have been able to shed light on the role of HER-2 for hormone-dependent tumor growth as well as cytotoxic drug activities.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2000
- Accession Number
- ADA398421
Entities
People
- Anton Wellstein
Organizations
- Georgetown University