BRCA1 up-regulation is associated with repair-mediated resistance to cis-diamminedichloroplatinum(II) Journal Article
| Authors: | Husain, A.; He, G.; Venkatraman, E. S.; Spriggs, D. R. |
| Article Title: | BRCA1 up-regulation is associated with repair-mediated resistance to cis-diamminedichloroplatinum(II) |
| Abstract: | 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. |
| Keywords: | controlled study; human cell; cisplatin; ovarian neoplasms; dna damage; cell cycle; dna repair; cancer susceptibility; apoptosis; gene product; cancer cell culture; drug resistance, neoplasm; tumor cells, cultured; breast neoplasms; brca1 protein; cancer resistance; oncogene; tumor suppressor gene; gene expression regulation, neoplastic; rna, messenger; genes, brca1; breast carcinoma; ovary carcinoma; up-regulation; rna, neoplasm; humans; human; female; priority journal; article |
| Journal Title: | Cancer Research |
| Volume: | 58 |
| Issue: | 6 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1998-03-15 |
| Start Page: | 1120 |
| End Page: | 1123 |
| Language: | English |
| PUBMED: | 9515792 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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