Transcription-Coupled Repair and Breast Cancer
Annual rept. 1 Jun 1998-31 May 1999
KENTUCKY UNIV RESEARCH FOUNDATION LEXINGTON
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We have focused on measuring the removal of ultraviolet UV light induced cyclobutane pyrimidine dimers CPD from the dyhydrofolate reductase gene DHFR in wild type and BRCA2 defective human cell lines to determine if BRCA2 gene defects impact transcription- coupled repair TCR in human cells. We have focused on characterizing TCR defects in human cells since other laboratories have focused on and documented TCR defects in mouse embryo fibroblast cell lines containing BRCA gene defects Gowan et al,1998. To extend these important findings we have investigated whether BRCA2 defects impact TCR in human cells by studying the Capan-1 cell line obtained from the American Type Culture Collection. Capan-1 contains a mutation in one allele of the BRCA2 gene and a deletion in the other allele Abbott et al, 1998. We have optimized conditions to measure TCR in human cells using a probe for the DHFR gene. We find that the Capan-I cell line undergoes what appears to be a form of cellular senescence and interpretation of repair results are complicated by the senescence phenotype. Hence, we have chosen to establish systems where we can introduce mutant and wild type copies of BRCA genes using an inducible expression system.
- Medicine and Medical Research