Procathepsin D Stimulation of Human Breast Cancer Cell Growth
Abstract
The long-term objective is to develop a new treatment for breast cancer based on blockade of the growth factor activity of procathepsin D. Breast cancer cells secrete procathepsin D, the enzymatically inactive form from which the aspartic proteinase cathepsin D is generated by removal of an activation peptide (APpCD). Procathepsin D has been identified as an independent prognostic factor in several forms of cancer. In preliminary experiments, procathepsin D was found to act as a specific autocrine growth factor for breast cancer-derived cells, but not for any other cell type tested. First sets of MDA-MD-231 cell line transfected with procathepsin D cDNA are currently tested. Preliminary results showed high level of procathepsin D secreation and thus suggested successful transfection. Experiments establishing the basic values in invasiveness of parental cell line and the effect of procathepsin D have been established. Similarly, the effect of inhibition of procathepsin D secretion in vivo has been demonstrated. All necessary synthetic peptides and fragments were synthesized. After establishing that the fragment 27-44 is the part of the activation peptide responsible for the binding to the cancer cells, we focused out attention on this particular part of the activation peptide. We prepared the library of 10 peptides which will be tested in vitro. The goal is to pinpoint the exact binding moiety on the activation peptide molecule.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA385640
Entities
People
- Vaclav Vetvicka
Organizations
- University of Louisville