role of the BRCA1-dependent DNA repair pathway in the pathogenesis of non-hereditary epithelial ovarian cancer.
Published: 2005
Language: eng
Number of pages: 72
Description: The BRCA1 protein is involved in the cellular response to DNA repair and has an essential role in the maintenance of genomic stability, and the inactivation of BRCA1 is believed to be an underlying mechanism in the pathogenesis of ovarian cancer. The ovarian carcinoma cell line, BG-1 was studied by comparing control (BG-1 NEO) and antisense (BG-1 AS) cells, in which the BRCA1 gene is expressed and inhibited respectively. Gene expression, related to the DNA damage response pathway, was examined using a GEarray, and cytogenetic profiles between the cell lines were compared by spectral karyotyping (SKY) and interphase fluorescence in situ hybridization (I-FISH) analysis. SKY and I-FISH analysis indicated there was a BRCA1-dependent increase in the frequency of structural, but not numerical chromosome aberrations in BG-1 AS in comparison to BG-1. Consistent with these observations, gene expression profiling showed significant overexpression of p53 and XRCC1, and underexpression of GADD45 in the BRCA1-deficient BG-1 AS cells. Inhibition of BRCA1 shows significant alterations in a number of genes involved in the DNA damage response and the genomic consequences reveal an elevated frequency of structural chromosomal instability.
Notes: Thesis (M.Sc.)--University of Toronto, 2005.

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Source: Masters Abstracts International, Volume: 44-01, page: 0323.

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