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AKT/mTOR 信号通路与人类脑胶质瘤恶性程度的关系。

Association between AKT/mTOR signalling pathway and malignancy grade of human gliomas.

机构信息

Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan City, 250012 Shandong Province, People's Republic of China.

出版信息

J Neurooncol. 2011 Jul;103(3):453-8. doi: 10.1007/s11060-010-0424-1. Epub 2010 Sep 29.

DOI:10.1007/s11060-010-0424-1
PMID:20878445
Abstract

The mammalian target of rapamycin (mTOR) signaling pathway has emerged as a major effector of cell growth and proliferation, and is an attractive target for cancer therapy. However, the association between mTOR pathway and the malignancy grade of human gliomas has not been thoroughly investigated. Tumor tissues from 87 Chinese patients (49 males, average age of 51.7 ± 13.0 years, range 15-78) with glioma were prospectively collected. The expression of three key proteins of the mTOR pathway, pAKT, pmTOR and p-p70S6 kinase (p-p70S6K) was measured by semi-quantitative immunohistochemical techniques. Grade I-II, III and IV glioma was pathologically identified in 27 (31.0%), 24 (27.6%) and 36 (41.4%) patients, respectively. Of the 87 patients, pAKT, pmTOR and p-p70S6K were found in 63 (72.4%), 65 (74.7%), and 63 (72.4%) patients, respectively. The expression of all three pAKT, pmTOR and p-p70S6K proteins was found in 42 (48.3%) patients, while only one or two of the three proteins were found in the remaining patients (51.7%). The percentage of patients with very strong expression of pAKT, pmTOR and p-p70S6K in grade IV glioma was 13 (36.1%), 16 (44.4%) and 15 (41.7%), respectively, which was greater than in grade I or II tumors (0-3.7%, P < 0.01). In conclusion, expression of mTOR pathway proteins pAKT, pmTOR and p-p70S6K can be found in human glioma of all malignancy grades. However, higher levels of these proteins were associated with advanced malignancy grades of the tumor.

摘要

哺乳动物雷帕霉素靶蛋白(mTOR)信号通路已成为细胞生长和增殖的主要效应因子,是癌症治疗的一个有吸引力的靶点。然而,mTOR 通路与人类脑胶质瘤恶性程度的关系尚未得到彻底研究。前瞻性收集了 87 例中国脑胶质瘤患者(49 例男性,平均年龄 51.7±13.0 岁,范围 15-78 岁)的肿瘤组织。采用半定量免疫组织化学技术检测 mTOR 通路的三个关键蛋白 pAKT、pmTOR 和 p-p70S6 激酶(p-p70S6K)的表达。病理上分别确定 27 例(31.0%)、24 例(27.6%)和 36 例(41.4%)为 I-II 级、III 级和 IV 级胶质瘤。在 87 例患者中,pAKT、pmTOR 和 p-p70S6K 的表达分别为 63 例(72.4%)、65 例(74.7%)和 63 例(72.4%)。在 42 例(48.3%)患者中发现所有三种 pAKT、pmTOR 和 p-p70S6K 蛋白表达,而在其余患者中仅发现一种或两种蛋白表达(51.7%)。IV 级胶质瘤患者中 pAKT、pmTOR 和 p-p70S6K 蛋白强表达的百分比分别为 13(36.1%)、16(44.4%)和 15(41.7%),高于 I 级或 II 级肿瘤(0-3.7%,P<0.01)。总之,mTOR 通路蛋白 pAKT、pmTOR 和 p-p70S6K 的表达可在所有恶性程度的人脑胶质瘤中发现。然而,这些蛋白的高水平与肿瘤恶性程度的进展有关。

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