Genes Determining Taxol Sensitivity
Abstract
To identify genes determining tumor cell sensitivity to taxol, we have carried out expression selection of genetic suppressor elements (GSEs) that would render cells resistant to taxol. Human cells were transduced with a retroviral library of normalized cDNA fragments, and several putative GSEs were isolated by consecutive rounds of taxol selection, recovery of integrated retroviruses and re-transduction of recipient cells. Based on the mitochondrial origin of one of the putative GSEs, we have developed cell lines lacking in mitochondrial DNA and found that such lines are cross-resistant to several drugs but not to taxol. The tested candidate GSEs conferred taxol resistance in some but not all experiments; this result most probably reflects a requirement for co-transduction of cells with some additional GSEs, as found in another OSE selection project. To improve future selection and testing of GSE combinations, we have developed novel retroviral vectors carrying green fluorescent protein as a marker gene, as well as methods for using such vectors and for efficient recovery of integrated retroviruses. Finally, we found that treatment of breast carcinoma cells with different anticancer agents induces a senescence-like phenotype associated with permanent growth arrest; augmentation of this response may be beneficial for breast cancer therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA381261
Entities
People
- Hongming Zhu
Organizations
- University of Illinois at Chicago