Paclitaxel (Taxol) Resistance in Breast Cancer Cells
Abstract
The development of resistance to taxanes is the major clinical limitation in using these agents for treating breast cancer. P-glycoprotein (P-gp) is a multidrug transporter, the product of the MDRl gene and the major known mechanism of resistance to taxanes. In this project we sought to identify non-MDR1 mechanisms of resistance by developing relevant cellular models. We developed models of both uterine sarcoma and breast cancer resistant to taxol alone (mediated by P-gp) and the combination of taxol with PSC 833, a potent inhibitor of F-gp. The uterine sarcoma cells showed changes in beta-tubulin isotype profiles whereas the breast cancer cells did not. Both cell types were demonstrated to have alterations in apoptotic proteins, specifically BCL-2 up regulation and BAX down regulation. Genomic profiling yielded numerous genetic differences between the selected variants, the significance of which needs further investigation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADA388126
Entities
People
- Branimir I. Sikic
Organizations
- Stanford University