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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

BRCA1 up-regulation is associated with repair-mediated resistance to cis-diamminedichloroplatinum(II).

We sought to identify novel genes associated with cis-diamminedichloroplatinum(II) ( CDDP) resistance, and by differential display analysis, we found that the human breast and ovarian cancer susceptibility gene BRCA1 was overexpressed in CDDP-resistant MCF-7 cells. A recent report that BRCA1 and human Rad51 colocalize in S-phase cells suggests a role for BRCA1 in DNA damage repair. We hypothesized that BRCA1 plays a role in DNA damage repair- mediated CDDP resistance. In CCDP-resistant variants of breast and ovarian carcinoma cell lines, MCF-7 CDDP/R and SKOV-3 CDDP/R, we found increased levels of BRCA1 protein, and we determined that the SKOV-3 CDDP/R cell line is significantly more proficient at DNA damage repair. Antisense inhibition of BRCA1 in this cell line resulted in an increased sensitivity to CDDP, a decreased proficiency of DNA repair, and an enhanced rate of apoptosis. These data support the hypothesis that BRCA1 is a gene involved in DNA damage repair.[1]


  1. BRCA1 up-regulation is associated with repair-mediated resistance to cis-diamminedichloroplatinum(II). Husain, A., He, G., Venkatraman, E.S., Spriggs, D.R. Cancer Res. (1998) [Pubmed]
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