Poly(ADP-ribose) polymerase-1 plays a role in suppressing mammary tumourigenesis in mice
| Autor: | Wei-Min Tong, Zhao-Qi Wang, Yun-Gui Yang, Lucien Frappart, W H Cao, D Galendo, Yan Shen |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Programmed cell death Tumor suppressor gene DNA repair DNA damage Poly ADP ribose polymerase Blotting Western Poly (ADP-Ribose) Polymerase-1 Fluorescent Antibody Technique Loss of Heterozygosity Biology medicine.disease_cause Mice chemistry.chemical_compound Transcription (biology) Genetics medicine Animals Molecular Biology Chromosome Aberrations BRCA1 Protein Mammary Neoplasms Experimental Cell Transformation Neoplastic chemistry Cancer research Female Poly(ADP-ribose) Polymerases Tumor Suppressor Protein p53 Carcinogenesis DNA |
| Zdroj: | Oncogene. 26:3857-3867 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1210156 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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