Expression and processing of the neuroendocrine protein secretogranin II in benign and malignant pheochromocytomas
Expression and processing of the neuroendocrine protein secretogranin II in benign and malignant pheochromocytomas
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DOI：
10.1196/annals.1353.056
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Yon, Laurent
中科院分区：
文献类型：
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作者：
Guillemot, Johann;Barbier, Laure;Yon, Laurent
本研究的目的是比较良性与恶性嗜铬细胞瘤中分泌颗粒素 It (SgII)、激素原转化酶（PC1 和 PC2）的表达水平以及 SgII 的蛋白水解加工。定量 (Q)-PCR 实验表明，与非肿瘤嗜铬细胞相比，SgII、PC1 和 PC2 mRNA 在嗜铬细胞瘤中过表达（P < 0.001）和良性肿瘤相比（P < 0.01），使用人 SgII 抗血清的蛋白质印迹分析显示出现了与 SgII 预期大小相对应的 97-kDa 带，良性肿瘤中的数量显着高于恶性肿瘤（P < 0.05）。观察到良性和恶性嗜铬细胞瘤之间不同的加工特征，相反，使用 PC1 和 PC2 抗血清，RIA 测量发现良性和恶性嗜铬细胞瘤之间的 EM66 中值显着不同，分别为 128.5 和 6.3 ng/mg 蛋白。综上所述，这些结果表明，在嗜铬细胞瘤中，恶性肿瘤与 PC1、PC2 和 SgII mRNA 表达减少以及 SgII 加工产物水平降低有关，这与恶性肿瘤中出现的低浓度 EM66 一致。这些数据支持这样的观点：SgII 加工产物（例如 EM66）可以代表嗜铬细胞瘤的预后标志物。
The aim of the present study was to compare the expression levels of secretogranin It (SgII), prohormone convertases (PC1 and PC2, and the proteolytic processing of SgII in benign versus malignant pheochromocytomas. Quantitative (Q)-PCR experiments indicated that SgII, PC1, and PC2 mRNAs were overexpressed in pheochromocytoma compared to non-tumoral chromaffin cells (P < 0.001) and in benign compared to malignant tumors (P < 0.01). Western blot analysis using a human SgII antiserum revealed the occurrence of a 97-kDa band corresponding to the expected size of SgII, with significantly higher quantities in benign than in malignant tumors (P < 0.05). Using antisera directed against sequential regions of SgII (N-terminal, secretoneurin [SN], EM66, internal, and C-terminal sequences), we observed distinct processing profiles between benign and malignant pheochromocytomas. In contrast, using PC1 and PC2 antisera no differences between the two types of tumors were found. RIA measurement showed that EM66 median values between benign and malignant chromaffin cell tumors were significantly different 128.5 vs. 6.3 ng/mg protein, respectively; P < 0.001). Taken together, these results indicate that, in pheochromocytoma, malignancy is associated with reduced PC1, PC2, and SgII mRNA expression and decreased levels of processing products of SgII, in line with the low concentrations of EM66 that occur in malignant tumors. These data support the notion that SgII-processing products, such as EM66, could represent prognostic markers of pheochromocytomas.