Werner Haim
Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Front Endocrinol (Lausanne). 2022 Mar 31;13:844575. doi: 10.3389/fendo.2022.844575. eCollection 2022.
The breast and ovarian cancer susceptibility gene (BRCA1) is a tumor suppressor whose mutation has been associated with the development of breast, ovarian and, probably, other malignancies at young ages. The BRCA1 gene product participates in multiple biological pathways including the DNA damage response, transcriptional control, cell growth and apoptosis. Inactivating germline mutations of the gene can be detected in a substantial portion of families with inherited breast and/or ovarian cancer. While the genomic and cancer-related actions of BRCA1 have been extensively investigated, not much information exists regarding the cellular and circulating factors involved in regulation of expression and action. The present review article dissects the emerging role of BRCA1 as an important regulator of various endocrine and metabolic axes. Experimental and clinical evidence links BRCA1 with a number of peptide and steroid hormones. Furthermore, comprehensive analyses identified complex interactions between the insulin/insulin-like growth factor-1 (IGF1) signaling axis and BRCA1. The correlation between metabolic disorders, including diabetes and the metabolic syndrome, and mutations, are discussed in this article.
乳腺癌和卵巢癌易感基因（BRCA1）是一种肿瘤抑制基因，其突变与年轻时患乳腺癌、卵巢癌以及可能的其他恶性肿瘤有关。BRCA1基因产物参与多种生物学途径，包括DNA损伤反应、转录调控、细胞生长和凋亡。在相当一部分遗传性乳腺癌和/或卵巢癌家族中可检测到该基因的种系失活突变。虽然BRCA1的基因组和癌症相关作用已得到广泛研究，但关于参与其表达和作用调控的细胞和循环因子的信息却不多。本综述文章剖析了BRCA1作为各种内分泌和代谢轴重要调节因子的新作用。实验和临床证据将BRCA1与多种肽类和类固醇激素联系起来。此外，综合分析确定了胰岛素/胰岛素样生长因子-1（IGF1）信号轴与BRCA1之间的复杂相互作用。本文还讨论了包括糖尿病和代谢综合征在内的代谢紊乱与BRCA1突变之间的相关性。
