Send to

Choose Destination
See comment in PubMed Commons below
Cancer Res. 1998 Mar 15;58(6):1120-3.

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

Author information

Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.


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.

[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center