| First Author | Tong WM | Year | 2007 |
| Journal | Oncogene | Volume | 26 |
| Issue | 26 | Pages | 3857-67 |
| PubMed ID | 17160013 | Mgi Jnum | J:122892 |
| Mgi Id | MGI:3715694 | Doi | 10.1038/sj.onc.1210156 |
| Citation | Tong WM, et al. (2007) Poly(ADP-ribose) polymerase-1 plays a role in suppressing mammary tumourigenesis in mice. Oncogene 26(26):3857-67 |
| abstractText | The DNA strand break-binding molecule, poly(ADP-ribose) polymerase-1 (PARP-1), plays a role in DNA repair, chromosomal stability, transcription and cell death. Accumulating evidence suggests that dysfunction of PARP-1 contributes to tumorigenesis. Here, we report that PARP-1 deficiency causes mammary carcinoma formation in female mice, and that the introduction of Trp53 mutations accelerates the onset and shortens the latency of mammary tumorigenesis. We show that PARP-1 deficiency results in chromosomal aneuploidy and centrosome amplification, which are substantiated by the inactivation of Trp53 in primary mammary epithelial (PME) cells. In addition, PARP-1 deficiency compromises p53 activation and impairs BRCA1 recruitment to the sites of DNA damage in PME cells. PARP-1 complementation partly rescues the defective DNA damage response mediated by p53 and BRCA1. The present study thus identifies a role of PARP-1 in suppressing mammary tumorigenesis in vivo and suggests that dysfunction of PARP-1 may be a risk factor for breast cancer in humans. |
