title: BRCA1 regulates PIG3-mediated apoptosis in a p53-dependent manner.
abstract: BRCA1 plays a key role in the regulation of p53-dependent target gene transcription activation. Meanwhile, the p53 inducible gene 3 (PIG3) is a downstream target of p53 and is involved in p53-initiated apoptosis. However, little is known about whether BRCA1 can regulate PIG3-mediated apoptosis. Using a tissue microarray containing 149 breast cancer patient samples, we found that BRCA1 and PIG3 expression status were significantly positively correlated (r = 0.678, P < 0.001) and identified a significant positive correlation between high expression of BRCA1 and/or PIG3 and overall survival (OS). Moreover, we reveal that overexpression of BRCA1 significantly increased expression of PIG3 in cells with intact p53, whereas no increase in PIG3 was observed in p53-null MDA-MB-157 cells and p53-depleted HCT116p53-/- cells. Meanwhile, ectopic expression of BRCA1 could not lead to an increase expression level of prohibitin (PHB), which we have previously identified to induce PIG3-mediated apoptosis. Finally, ChIP analysis revealed that PHB can bind to the PIG3 promoter and activate PIG3 transcription independent of p53, although p53 presence did enhance this process. Taken together, our findings suggest that BRCA1 regulates PIG3-mediated apoptosis in a p53-dependent manner, and that PIG3 expression is associated with a better OS in breast cancer patients.
authors: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.
authors: Wenwen
authors: W
authors: Zhang
authors: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.
authors: Jiayan
authors: J
authors: Luo
authors: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.
authors: Fengxia
authors: F
authors: Chen
authors: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.
authors: Fang
authors: F
authors: Yang
authors: Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou 510282, China.
authors: Wei
authors: W
authors: Song
authors: Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou 510282, China.
authors: Aiyu
authors: A
authors: Zhu
authors: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.|Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou 510282, China.
authors: Xiaoxiang
authors: X
authors: Guan
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D019398:Genes, BRCA1 / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D000091402:Prohibitins; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C000717328:PHB protein, human; D000091402:Prohibitins; D011518:Proto-Oncogene Proteins; C411296:TP53I3 protein, human; D016159:Tumor Suppressor Protein p53
keywords: BRCA1; PIG3; breast cancer; p53; prohibitin