Matsutani N, Yokozaki H, Tahara E, Tahara H, Kuniyasu H, Kitadai Y, Haruma K, Chayama K, Tahara E, Yasui W
First Department of Pathology, Hiroshima University School of Medicine, Minami-ku, Hiroshima, Japan.
Pathobiology. 2001;69(4):219-24. doi: 10.1159/000055946.
The MRE11 complex (MRE11, RAD50, NBS1) are required for the repair of DNA double-strand breaks and have another important function in regulating telomere length. The silent information regulator (Sir) proteins required for telomere position effect also bind telomeres. hRap1 protein is a human ortholog of yeast Rap1 which regulates telomere length by interacting with TRF2 and is recruited to telomeres by TRF2. We examined the expression of the MRE11 complex (MRE11, RAD50, NBS1), Sir2 and hRAP1 in 20 gastric carcinomas by reverse transcription polymerase chain reaction and then analyzed the relation between telomerase activity and other telomerase components such as human telomerase reverse transcriptase (TERT), human telomerase RNA component (hTR), human telomerase-associated protein (TEP1), telomeric repeat binding factor 1 (TRF1), TRF2- and TRF1-interacting, ankyrin-related ADP-ribose polymerase (tankyrase) as well as TRF1-interacting nuclear protein 2 (TIN2). Of twenty gastric carcinomas examined, 13 (65%), 14 (70%), 16 (80%), 12 (60%) and 13 (65%) expressed MRE11, RAD50, NBS1, Sir2 and hRap1 at higher levels than corresponding nonneoplastic gastric mucosa, respectively. No obvious correlation was observed between MRE11 complex expression and telomerase activity or expression of TERT, hTR, TEP1, tankyrase and TIN2. Carcinomas with high TRF1 expression expressed significantly higher levels of MRE11 and RAD50 than those with low TRF1 expression (p < 0.05). On the other hand, carcinomas with high TRF2 expression expressed significantly higher levels of MRE11, NBS1 and hRap1 than those with low TRF2 expression (p < 0.05). These results suggest that gastric carcinomas with high TRF1 and TRF2 expression may need a large quantity of the MRE11 complex. Moreover, gastric carcinomas with high TRF1 expression may require a large quantity of hRap1.
MRE11复合物（MRE11、RAD50、NBS1）是DNA双链断裂修复所必需的，并且在调节端粒长度方面具有另一个重要功能。端粒位置效应所需的沉默信息调节因子（Sir）蛋白也结合端粒。hRap1蛋白是酵母Rap1的人类同源物，它通过与TRF2相互作用来调节端粒长度，并由TRF2招募至端粒。我们通过逆转录聚合酶链反应检测了20例胃癌中MRE11复合物（MRE11、RAD50、NBS1）、Sir2和hRAP1的表达，然后分析了端粒酶活性与其他端粒酶组分之间的关系，这些组分包括人类端粒酶逆转录酶（TERT）、人类端粒酶RNA组分（hTR）、人类端粒酶相关蛋白（TEP1）、端粒重复结合因子1（TRF1）、TRF2与TRF1相互作用的锚蛋白相关ADP核糖聚合酶（端粒酶）以及TRF1相互作用核蛋白2（TIN2）。在检测的20例胃癌中，13例（65%）、14例（70%）、16例（80%）、12例（60%）和13例（65%）的MRE11、RAD50、NBS1、Sir2和hRap1表达水平分别高于相应的非肿瘤性胃黏膜。未观察到MRE11复合物表达与端粒酶活性或TERT、hTR、TEP1、端粒酶和TIN2表达之间存在明显相关性。TRF1高表达的癌组织中MRE11和RAD50的表达水平显著高于TRF1低表达的癌组织（p < 0.05）。另一方面，TRF2高表达的癌组织中MRE11、NBS1和hRap1的表达水平显著高于TRF2低表达的癌组织（p < 0.05）。这些结果表明，TRF1和TRF2高表达的胃癌可能需要大量的MRE11复合物。此外，TRF1高表达的胃癌可能需要大量的hRap1。
