Martínez-Arribas Fernando, Agudo David, Pollán Marina, Gómez-Esquer Francisco, Díaz-Gil Gema, Lucas Raul, Schneider José
Fundación Tejerina-Centro de Patología de la Mama, Madrid, Spain.
J Cell Biochem. 2006 Apr 15;97(6):1275-82. doi: 10.1002/jcb.20725.
In a recent report, it has been postulated that the ubiquitous RBM proteins might constitute a novel family of apoptosis modulators. We measured the expression of the X-chromosome RBM genes (RBMX, RBM3, and RBM10) in 122 breast cancers by means of differential RT-PCR. Using the same method, we also studied the expression of the apoptosis-related genes Bcl-2 and Bax. Markers of hormone dependence (estrogen and progesterone receptors), proliferation (Ki67 and DNA-ploidy), angiogenesis (VEGF and CD105), as well as oncogene (c-erb-B2), and tumor suppressor gene (p53) expression were also analyzed. The expression of all X-chromosome RBM genes was significantly associated with the expression of the proapoptotic Bax gene (RBMX, P=0.039; RBM3, P<0.001; RBM10 large variant, P<0.001; RBM10 small variant, P<0.001). Furthermore, the expression of both RBM10 variants was significantly associated with the expression of the VEGF gene (large variant, P=0.004; small variant, P=0.003). We also found an association of borderline significance (P=0.05) between the expression of RBM3, the large variant of RBM10 and wild-type p53. Expression of the small RBM10 variant, finally, was associated with high proliferation of the tumors (Ki67>or=20%; P=0.037). The expression of both RBM10 variants seems to be interdependent to a significant degree (r=0.26, P=0.006). From these results, it seems that the X-chromosome, through its RBM genes, plays a formerly unknown role in the regulation of programmed cell death (apoptosis) in breast cancer.
在最近的一份报告中,有人推测普遍存在的RBM蛋白可能构成一个新的凋亡调节因子家族。我们通过差异逆转录聚合酶链反应(differential RT-PCR)检测了122例乳腺癌中X染色体RBM基因(RBMX、RBM3和RBM10)的表达。使用相同的方法,我们还研究了凋亡相关基因Bcl-2和Bax的表达。此外,还分析了激素依赖性标志物(雌激素和孕激素受体)、增殖标志物(Ki67和DNA倍体)、血管生成标志物(VEGF和CD-105)以及癌基因(c-erb-B2)和肿瘤抑制基因(p53)的表达。所有X染色体RBM基因的表达均与促凋亡Bax基因的表达显著相关(RBMX,P=0.039;RBM3,P<0.001;RBM10大变异体,P<0.001;RBM10小变异体,P<0.001)。此外,RBM10两个变异体的表达均与VEGF基因的表达显著相关(大变异体,P=0.004;小变异体,P=0.003)。我们还发现RBM3、RBM10大变异体与野生型p53的表达之间存在临界显著性关联(P=0.05)。最后,RBM10小变异体的表达与肿瘤的高增殖相关(Ki67≥20%;P=0.037)。RBM10两个变异体的表达在很大程度上似乎相互依赖(r=0.26,P=0.006)。从这些结果来看,X染色体似乎通过其RBM基因在乳腺癌程序性细胞死亡(凋亡)的调节中发挥了以前未知的作用。