Boltze Carsten, Mundschenk Jochen, Unger Nicole, Schneider-Stock Regine, Peters Brigitte, Mawrin Christian, Hoang-Vu Cuong, Roessner Albert, Lehnert Hendrik
Department of Pathology,Otto von Guericke University, D-39120 Magdeburg, Germany.
J Clin Endocrinol Metab. 2003 Sep;88(9):4280-6. doi: 10.1210/jc.2002-021299.
Telomerase, a ribonucleoprotein complex that includes the telomerase RNA component, the telomerase-associated protein (TP1), the telomerase catalytic subunit (hTERT), and the heat shock protein 90 (HSP90), is closely related to the malignant potential of human tumors. In pheochromocytomas (PC) it is very difficult to predict malignant potential by conventional histology or immunohistochemical and molecular markers. To test whether the expression of telomerase subunits is reflected in the malignant transition of PCs, we determined their mRNA and/or protein expression in 28 benign and nine malignant PCs and compared the results with telomerase activity. RT-PCR analysis revealed that TP1 was ubiquitously expressed. The telomerase RNA component was found in all malignant (100%) and in 13 of 28 (46%) benign PCs. In contrast, hTERT was clearly associated with aggressive biological behavior. All of the malignant (100%), but only two of 28 benign (7%) PCs expressed hTERT. HSP90 was increased in malignant PCs, but was also expressed at a lower level in benign tumors. High telomerase activity was measurable in hTERT-positive tissues only. Our data indicate that hTERT, HSP90, and telomerase activity are up-regulated in malignant cells of the adrenal medulla. The common expression of hTERT and telomerase activity thus represents an additional prognostic marker that may identify more aggressive tumors.
端粒酶是一种核糖核蛋白复合体，包括端粒酶RNA组分、端粒酶相关蛋白（TP1）、端粒酶催化亚基（hTERT）和热休克蛋白90（HSP90），它与人类肿瘤的恶性潜能密切相关。在嗜铬细胞瘤（PC）中，通过传统组织学或免疫组化及分子标志物很难预测其恶性潜能。为了检测端粒酶亚基的表达是否反映在PC的恶性转变中，我们测定了28例良性和9例恶性PC中端粒酶亚基的mRNA和/或蛋白表达，并将结果与端粒酶活性进行比较。逆转录聚合酶链反应（RT-PCR）分析显示TP1普遍表达。端粒酶RNA组分在所有恶性PC（100%）以及28例良性PC中的13例（46%）中被检测到。相比之下，hTERT与侵袭性生物学行为明显相关。所有恶性PC（100%）均表达hTERT，但28例良性PC中只有2例（7%）表达hTERT。HSP90在恶性PC中表达增加，但在良性肿瘤中也有较低水平的表达。仅在hTERT阳性组织中可检测到高端粒酶活性。我们的数据表明，hTERT、HSP90和端粒酶活性在肾上腺髓质的恶性细胞中上调。hTERT和端粒酶活性的共同表达因此代表了一种额外的预后标志物，可能有助于识别更具侵袭性的肿瘤。
