DNA damage induces BRCA1 distribution alteration in prostate cancer cell lines / 中华男科学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the role of the tumor suppressor gene BRCA1 in response to DNA damage and to confirm that the function of the BRCA1 protein is regulated by a variety of mechanisms including transcriptional control, phosphorylation and protein-protein interaction.</p><p><b>METHODS</b>With the human breast cell line MCF7 as the positive control, we determined the subcellular distribution of BRCA1 in the prostate cancer cell lines LNCaP, DU145 and PC3 by immunohistochemical staining and Western blotting analyses.</p><p><b>RESULTS</b>BRCA1 was present in the prostate cancer cell lines LNCaP, DU145 and PC3. Ionizing radiation induced BRCA1 nuclear export, increasing from 14% to 40% in the cytoplasma (P < 0.01) and decreasing from 46% to 21% in the nuclei (P < 0.01). This DNA damage-induced BRCA1 nuclear export occurred only in the p53 wild-type but not in the p53 mutant cell line. The apoptosis rate of LNCaP cells was as high as 40% after nuclear export, with an obvious increase of cleaved caspase-3, which was correlated with BRCA1 nuclear-cytoplasmic shuttling.</p><p><b>CONCLUSION</b>Cytoplasmic relocalization of the BRCA1 protein may be a mechanism whereby the BRCA1 function is regulated in response to DNA damage. Its induction of a higher rate of cell apoptosis indicates BRCA1 to be another good biomarker for the treatment of prostate cancer.</p>