Takaoka Miho, Miki Yoshio
Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Department of Genetic Diagnosis, The Cancer Institute, Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
Int J Clin Oncol. 2018 Feb;23(1):36-44. doi: 10.1007/s10147-017-1182-2. Epub 2017 Sep 7.
The BRCA1 protein, a hereditary breast and ovarian cancer-causing gene product, is known as a multifunctional protein that performs various functions in cells. It is well known, along with BRCA 2, to cause hereditary breast and ovarian cancer, but here we will specifically focus on BRCA1. We introduce the mechanism and the latest report on homologous recombination repair, replication, involvement in checkpoint regulation, transcription, chromatin remodeling, and cytoplasmic function (centrosome regulation, apoptosis, selective autophagy), and consider the possibility of carcinogenesis from inhibition of the intracellular functions in each. We also consider the possibility of drug development based on each function. Finally, we will explain, from data obtained through basic research, that an appropriate regimen is important for raising the response rate for poly (ADP)-ribose polymerase inhibitors, in the case of low susceptibility, iatrogenic toxicity, tolerance, etc.
BRCA1蛋白是一种导致遗传性乳腺癌和卵巢癌的基因产物，是一种在细胞中执行多种功能的多功能蛋白。它与BRCA2一样，众所周知会导致遗传性乳腺癌和卵巢癌，但在这里我们将特别关注BRCA1。我们介绍了同源重组修复、复制、参与检查点调节、转录、染色质重塑和细胞质功能（中心体调节、凋亡、选择性自噬）的机制和最新报告，并考虑了每种细胞内功能受到抑制导致致癌的可能性。我们还考虑了基于每种功能进行药物开发的可能性。最后，我们将根据基础研究获得的数据解释，在低敏感性、医源性毒性、耐受性等情况下，适当的治疗方案对于提高聚（ADP）-核糖聚合酶抑制剂的反应率很重要。
