HSP90 is a key for telomerase activation and malignant transition in pheochromocytoma (Retracted Article. See vol 23, pg 229, 2004)
HSP90 is a key for telomerase activation and malignant transition in pheochromocytoma (Retracted Article. See vol 23, pg 229, 2004)
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DOI：
10.1385/endo:22:3:193
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发表时间：
2003-12-01
期刊：
影响因子：
3.7
通讯作者：
Roessner, A
中科院分区：
文献类型：
--
作者：
Boltze, C;Lehnert, H;Roessner, A
最近对数量有限的嗜铬细胞瘤(PC)的研究揭示了端粒酶在这些肿瘤的恶性转化中的潜在作用。端粒酶是一种核糖核蛋白复合体，包括端粒酶RNA组分(M)、端粒酶相关蛋白(TP1)、端粒酶催化亚单位(HTERT)和热休克蛋白90(HSP90)。这些亚基之间的相互作用和端粒酶的激活机制仍然不清楚。为了验证端粒酶亚基的表达和调控是否反映在PC的恶变过程中，我们检测了28例良性PC和9例恶性PC中端粒酶亚基的表达，并与端粒酶活性进行了比较。逆转录聚合酶链式反应分析表明，TP1在细胞内普遍表达。HTR在所有恶性PC(100%)和13/28(46%)良性PC中均有表达。相比之下，端粒酶逆转录酶明显与攻击性生物行为有关。所有恶性PC(100%)均表达hTERT，良性PC中仅2例(7%)表达hTERT。HSP90在恶性PC中表达升高，而在良性肿瘤中表达较低。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。HSP90的过表达是hTERT激活端粒酶的重要因素。因此，hTERT和端粒酶活性的共同表达代表了一个额外的预后标志物，可以识别更具侵袭性的肿瘤。
Recent studies on a limited number of pheochromocytomas (PCs) revealed a potential role of telomerase in the malignant transition of these tumors. Telomerase is a ribonucleoprotein complex that includes the telomerase RNA component (M), the telomerase-associated protein (TP1), the telomerase catalytic subunit (hTERT), and the heat-shock protein 90 (HSP90). The interactions between these subunits and the activation machinery of telomerase are still unclear. To test whether the expression and regulation of telomerase subunits are reflected in the malignant transition of PCs, we determined their mRNA and/or protein expression in 28 benign and 9 malignant PCs and compared the results with telomerase activity. Reverse transcriptase polymerase chain reaction analysis revealed that TP1 was ubiquitously expressed. hTR was found in all malignant (100%) and in 13/28 (46%) benign PCs. By contrast, hTERT was clearly associated with aggressive biologic behavior. All the malignant (100%) but only 2/28 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 only hTERT-positive tissues. Our data indicate that hTERT, HSP90, and telomerase activity are upregulated in malignant cells of the adrenal medulla. Overexpression of HSP90 is an important factor in the activation of telomerase via hTERT. The common expression of hTERT and telomerase activity thus represents an additional prognostic marker that may identify more aggressive tumors.