Miyachi K, Fujita M, Tanaka N, Sasaki K, Sunagawa M
First Dept of Surgery, Dokkyo University School of Medicine, Tochigi, Japan.
J Exp Clin Cancer Res. 2002 Jun;21(2):269-75.
Telomeres of a specific length are essential for continuous cell proliferation. The length of telomeres must be maintained by telomerase action and the telomeric DNA-repeat binding protein must be protected. Therefore, there seems to be a relationship between cell immortality due to telomerase activity and telomeric DNA-repeat binding protein. We examined telomerase activity and the expression of telomeric-repeat binding factor 1 and 2 (TRF1 and TRF2) in gastric cancer. Telomerase activity was semi-quantified using the f-TRAP technique in 53 cancerous and non-cancerous gastric tissue specimens. TRF1 and TRF2 were also studied using an immunohistochemical method to determine the frequency of these factors in cell nuclei. Telomerase activity was observed in 79.2% of the cancerous tissue and in 39.6% of the non-cancerous tissue. The average semi-quantitative values for telomerase activity were 67.3 total product generated (TPG) unit/microg protein in cancerous tissue and 6.0 TPG unit/microg protein in non-cancerous tissue. Moreover, T0/1 tumor had the same incidence of telomerase activity as T2 or deeper tumors. These results indicated that the activation of telomerase begins at an early stage of carcinogenesis. TRF1 and TRF2 were detected in 45.1% and 42.9% of the cancerous tissue and in 70.6% and 65.6% of the non-cancerous tissue, respectively. In addition, low positive staining ratios were found for TRF1 and TRF2 when cancer had more deeply invaded. However, telomerase activity did not correlate with either TRF1 or TRF2. These findings suggest that optimal conditions for efficient telomerase are produced as cancer progresses, via suppression of TRFs.
特定长度的端粒对于细胞的持续增殖至关重要。端粒的长度必须通过端粒酶的作用来维持，并且端粒DNA重复序列结合蛋白必须得到保护。因此，端粒酶活性导致的细胞永生与端粒DNA重复序列结合蛋白之间似乎存在某种关系。我们检测了胃癌中端粒酶活性以及端粒重复序列结合因子1和2（TRF1和TRF2）的表达。采用f-TRAP技术对53例胃癌组织和非癌胃组织标本中的端粒酶活性进行半定量分析。同时采用免疫组化方法研究TRF1和TRF2，以确定这些因子在细胞核中的出现频率。在79.2%的癌组织和39.6%的非癌组织中观察到端粒酶活性。癌组织中端粒酶活性的平均半定量值为67.3个总产物生成（TPG）单位/微克蛋白，非癌组织为6.0 TPG单位/微克蛋白。此外，T0/1期肿瘤中端粒酶活性的发生率与T2期或更深层肿瘤相同。这些结果表明，端粒酶的激活在癌变早期就已开始。TRF1和TRF2分别在45.1%的癌组织和70.6%的非癌组织中被检测到，在42.9%的癌组织和65.6%的非癌组织中被检测到。此外，当癌症浸润更深时，TRF1和TRF2的阳性染色率较低。然而，端粒酶活性与TRF1或TRF2均无相关性。这些发现表明，随着癌症进展，通过抑制TRFs可产生有利于端粒酶高效发挥作用的最佳条件。
