Accession Number : ADA332864
Title : Genes Determining Taxol Sensitivity
Descriptive Note : Annual rept. 1 Aug 96-31 Jul 97
Corporate Author : ILLINOIS UNIV AT THE MEDICAL CENTER CHICAGO
Personal Author(s) : Kandel, Eugene
PDF Url : ADA332864
Report Date : SEP 1997
Pagination or Media Count : 22
Abstract : Taxol is a new potent chemotherapeutic agent for the treatment of metastatic breast cancer. However, many tumors show partial or complete resistance to taxol therapy. Biological mechanisms modulating taxol response in human cells are mostly unknown. A better understanding of molecular determinants of taxol response may lead to therapeutic strategies designed to prevent or overcome drug resistance. I am using a methodology based on genetic suppressor elements (GSEs) to identity molecular mechanisms of taxol response. An equal abundance small fragment library in a retroviral vector has been constructed in our laboratory from total human cDNA. I used this library to select GSEs conferring taxol resistance in human cells. After three rounds of infection, selection and insert recovery, putative GSEs were identified. These sequences are undergoing additional testing in human breast carcinoma cells. A rapid and efficient method for recovery and regeneration of integrated proviruses has been developed in the course of this selection and was shown to accurately maintain the complexity of retroviral population. I constructed a series of retroviral vectors with various forms of green fluorescent protein as a marker for transduction. Use of these vectors avoids common artifacts associated with other marker genes, and provide sensitive means to monitor the biological activities of transduced sequences. A new library in one of this vectors is now available for future selections on breast carcinoma cells.
Descriptors : *GENETIC ENGINEERING, *CHEMOTHERAPEUTIC AGENTS, *BREAST CANCER, NEOPLASMS, DRUGS, GENETIC MAPPING, MAMMARY GLANDS, SUPPRESSORS, RETROVIRUSES, METASTASIS.
Subject Categories : Genetic Engineering and Molecular Biology
Medicine and Medical Research
Distribution Statement : APPROVED FOR PUBLIC RELEASE