Flores Mauricio, Goodrich David W
Roswell Park Comprehensive Cancer Center, Department of Pharmacology and Therapeutics, Buffalo, NY, United States.
Front Genet. 2022 Mar 18;13:818719. doi: 10.3389/fgene.2022.818719. eCollection 2022.
The retinoblastoma susceptibility gene () is the first tumor suppressor gene discovered and a prototype for understanding regulatory networks that function in opposition to oncogenic stimuli. More than 3 decades of research has firmly established a widespread and prominent role for in human cancer. Yet, this gene encodes but one of three structurally and functionally related proteins that comprise the pocket protein family. A central question in the field is whether the additional genes in this family, and , are important tumor suppressor genes. If so, how does their tumor suppressor activity overlap or differ from . Here we revisit these questions by reviewing relevant data from human cancer genome sequencing studies that have been rapidly accumulating in recent years as well as pertinent functional studies in genetically engineered mice. We conclude that and do have important tumor suppressor activity in some contexts, but remains the dominant tumor suppressor in the family. Given their similarities, we speculate on why tumor suppressor activity is unique.
视网膜母细胞瘤易感基因（）是首个被发现的肿瘤抑制基因，也是理解与致癌刺激相对抗的调控网络的一个范例。三十多年的研究已确凿证实了其在人类癌症中广泛且显著的作用。然而，该基因仅编码构成口袋蛋白家族的三种结构和功能相关蛋白之一。该领域的一个核心问题是，这个家族中的另外两个基因，即 和 ，是否为重要的肿瘤抑制基因。如果是，它们的肿瘤抑制活性与 如何重叠或不同。在此，我们通过回顾近年来迅速积累的人类癌症基因组测序研究的相关数据以及基因工程小鼠的相关功能研究，重新审视这些问题。我们得出结论，在某些情况下， 和 确实具有重要的肿瘤抑制活性，但 仍是该家族中主要的肿瘤抑制基因。鉴于它们的相似性，我们推测 肿瘤抑制活性独特的原因。
