Division of Hematology and Oncology, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
J Transl Med. 2011 Dec 14;9:213. doi: 10.1186/1479-5876-9-213.
BORIS, or CTCFL, the so called Brother of the Regulator of Imprinted Sites because of the extensive homology in the central DNA binding region of the protein to the related regulator, CTCF, is expressed in early gametogenesis and in multiple cancers but not in differentiated somatic cells. Thus it is a member of the cancer testes antigen group (CTAs). Since BORIS and CTCF target common DNA binding sites, these proteins function on two levels, the first level is their regulation via the methylation context of the DNA target site and the second level is their distinct and different epigenetic associations due to differences in the non-homologous termini of the proteins. The regulation on both of these levels is extensive and complex and the sphere of influence of each of these proteins is associated with vastly different cellular signaling processes. On the level of gene expression, BORIS has three known promoters and multiple spliced mRNAs which adds another level of complexity to this intriguing regulator. BORIS expression is observed in the majority of cancer tissues and cell lines analyzed up to today. The expression profile and essential role of BORIS in cancer make this molecule very attractive target for cancer immunotherapy. This review summarizes what is known about BORIS regarding its expression, structure, and function and then presents some theoretical considerations with respect to its genome wide influence and its potential for use as a vaccine for cancer immunotherapy.
BORIS，也称为 CTCFL，由于其蛋白中央 DNA 结合区域与相关调控因子 CTCF 具有广泛的同源性，故被称为印记位点调控因子的兄弟。BORIS 在早期配子发生和多种癌症中表达，但在分化的体细胞中不表达。因此，它是癌症睾丸抗原（CTA）家族的一员。由于 BORIS 和 CTCF 靶向共同的 DNA 结合位点，这些蛋白在两个层面上发挥作用，第一个层面是通过 DNA 靶位点的甲基化背景进行调控，第二个层面是由于蛋白非同源末端的差异而导致的独特和不同的表观遗传关联。这两个层面的调控非常广泛和复杂，这些蛋白的影响范围与截然不同的细胞信号转导过程有关。在基因表达水平上，BORIS 有三个已知的启动子和多个拼接的 mRNA，这为这个有趣的调控因子增加了另一层复杂性。迄今为止，在分析的大多数癌症组织和细胞系中都观察到 BORIS 的表达。BORIS 在癌症中的表达谱和重要作用使该分子成为癌症免疫治疗的极具吸引力的靶标。这篇综述总结了关于 BORIS 的表达、结构和功能的已知信息，然后提出了一些关于其全基因组影响及其作为癌症免疫治疗疫苗的潜在用途的理论考虑。
