Tumour Biology Group, Department of Research, Regional Cancer Program of the Hôpital Régional de Sudbury Regional Hospital, 41 Ramsey Lake Road, Sudbury, Ontario P3E 5J1, Canada.
J Thorac Oncol. 2010 Mar;5(3):294-8. doi: 10.1097/JTO.0b013e3181c6e330.
RBM5 is one member of a group of structurally related genes that includes RBM6 and RBM10. RBM10 maps to Xp11.23, and one allele is inactivated as a result of X chromosome inactivation. Both RBM5 and RBM6 map to 3p21.3, a tumor suppressor region that experiences loss of heterozygosity in the majority of lung cancers. Overexpression of RBM5, which encodes an RNA-binding protein involved in the regulation of alternative splicing and retards ascites associated tumor growth in immunocompromised mice, a phenomenon that may be related to an associated ability to modulate apoptosis. As part of our quest to gain a better understanding of how the proapoptotic activity of RBM5 might contribute to tumor suppressor function, we reviewed all the literature relating to RBM5 expression, with a focus on lung cancer. On the basis of the existing data, we suggest that-to more thoroughly assess the potential involvement of RBM5 as a lung cancer regulatory protein-more research is required regarding (a) the expression of not only full-length RBM5 but all of the alternate variants associated with the locus, in relation to histologic subtype and smoking history, and (b) the mutation status of various genes within the transforming growth factor-alpha signaling pathway, which may function to either directly or indirectly regulate RBM5 activity in RBM5-retaining lung cancers.
RBM5 是一组结构相关基因的成员之一，包括 RBM6 和 RBM10。RBM10 定位于 Xp11.23，一个等位基因由于 X 染色体失活而失活。RBM5 和 RBM6 均定位于 3p21.3，这是一个肿瘤抑制区域，在大多数肺癌中经历杂合性丢失。RBM5 编码一种参与调节选择性剪接的 RNA 结合蛋白，其过表达会减缓免疫缺陷小鼠中的腹水相关肿瘤生长，这一现象可能与相关的凋亡调节能力有关。作为我们深入了解 RBM5 的促凋亡活性如何促进肿瘤抑制功能的一部分，我们回顾了所有与 RBM5 表达相关的文献，重点是肺癌。基于现有数据，我们建议——为了更彻底地评估 RBM5 作为肺癌调节蛋白的潜在作用——需要更多的研究来关注（a）不仅全长 RBM5 的表达，而且与组织学亚型和吸烟史相关的所有与该基因座相关的替代变体的表达，以及（b）转化生长因子-α信号通路内的各种基因的突变状态，这些基因可能直接或间接调节 RBM5 活性在保留 RBM5 的肺癌中。
