Usselmann B, Portsmouth D, Barclay J, Morris A G, Nwokolo C U
Department of Gastroenterology, University Hospitals Coventry and Warwickshire NHS Trust, UK.
Dig Dis Sci. 2001 Dec;46(12):2666-72. doi: 10.1023/a:1012767127278.
Increased expression of telomerase is critical in the pathogenesis of cancer. Telomerase expression is reported variably in foregut cancers, possibly as a result of telomerase inhibition or ribonucleases. We performed experiments to assess telomerase and telomerase RNA expression in foregut cancers and to quantify and characterize telomerase inhibition. Cancer specimens were obtained from 27 patients. Telomerase activity of cancers was determined by the telomeric repeat amplification protocol, the presence of telomerase RNA component (hTERC) by reverse transcription PCR, and the quantity of telomerase inhibitors in mixing experiments. Ribonuclease activity was measured by assessing degradation of labeled RNA by cancers. Telomerase was found in 8/11 adenocarcinomas of the esophagus or gastroesophageal junction and 6/16 distal gastric adenocarcinomas; hTERC was detectable in all cancers. Telomerase inhibition was more marked in distal compared to proximal adenocarcinomas (P = 0.01) and correlated with ribonuclease activity (rS = 0.65). Ribonucleases contribute significantly to telomerase inhibitory activity detectable in foregut cancer specimens. In vitro, the presence of telomerase inhibitors in some specimens did not prevent the detection of telomerase by the TRAP assay. This suggests a more complex relationship between telomerase and its inhibitors. Site-specificity of telomerase inhibitors generally and ribonuclease activity specifically suggests a putative regulatory role in vivo.
端粒酶表达增加在癌症发病机制中至关重要。在前肠癌症中端粒酶表达的报道存在差异，这可能是端粒酶抑制或核糖核酸酶作用的结果。我们进行了实验以评估前肠癌症中端粒酶和端粒酶RNA的表达，并对端粒酶抑制进行定量和表征。从27例患者获取癌症标本。通过端粒重复序列扩增法测定癌症的端粒酶活性，通过逆转录PCR检测端粒酶RNA组分（hTERC）的存在，并在混合实验中测定端粒酶抑制剂的量。通过评估癌症对标记RNA的降解来测量核糖核酸酶活性。在11例食管或胃食管交界腺癌中有8例检测到端粒酶，在16例远端胃腺癌中有6例检测到；在所有癌症中均可检测到hTERC。与近端腺癌相比，远端腺癌中端粒酶抑制更为明显（P = 0.01），且与核糖核酸酶活性相关（rS = 0.65）。核糖核酸酶对在前肠癌症标本中可检测到的端粒酶抑制活性有显著贡献。在体外，一些标本中端粒酶抑制剂的存在并未阻止通过端粒重复序列扩增法检测到端粒酶。这表明端粒酶与其抑制剂之间存在更复杂的关系。端粒酶抑制剂的位点特异性以及核糖核酸酶活性的位点特异性一般表明其在体内具有假定的调节作用。
