Correlation of proto-oncogene expression and proliferation and meningiomas.
Correlation of proto-oncogene expression and proliferation and meningiomas.
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DOI：
10.1097/00006123-199312000-00015
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发表时间：
1993-12
期刊：
影响因子：
4.8
通讯作者：
Allah Detta;Brendan G. Kenny;Conrad Smith;Ann Logan;Edward Hitchcock
中科院分区：
文献类型：
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作者：
Allah Detta;Brendan G. Kenny;Conrad Smith;Ann Logan;Edward Hitchcock
本文分析了19例典型和非典型组织学脑膜瘤的增殖和原癌基因表达，试图了解这些肿瘤生长过程的机制。通过体外溴脱氧尿苷照射肿瘤组织印迹中s期细胞的计数，估计增殖指数为增殖指数，并通过信使核糖核酸斑点杂交法定量检测c-myc、c-fos、c-src、c-H-ras、N-myc、酸性和碱性成纤维细胞生长因子、胰岛素样生长因子I和II、血小板源性生长因子α和表皮生长因子的基因表达。非典型肿瘤和恶性肿瘤的增殖指数明显高于非恶性肿瘤。c-myc和c-fos信使核糖核酸水平分别在72%和78%的肿瘤中升高了5倍以上，相对于该系列中检测到的最低水平。生长因子信使核糖核酸水平零星升高；37 - 44%的肿瘤中酸性和碱性成纤维细胞生长因子水平提高了5倍以上。在非典型/恶性肿瘤中发现c-myc增殖与原癌基因/生长因子表达呈正相关，在成纤维细胞脑膜瘤中发现表皮生长因子表达正相关。典型和非典型肿瘤中常见的c-myc和c-fos的不正常表达表明，这些是脑膜瘤肿瘤过程中的早期事件，可能扰乱细胞分化的控制，并与成纤维细胞生长因子一起，可能通过减少对外源有丝分裂原的需求，并为肿瘤克隆的生长提供一个生态位，从而赋予转化细胞选择性生长优势。c-myc水平与非典型/恶性脑膜瘤的增殖呈正相关，这表明这是恶性肿瘤的一个特征，表明在肿瘤进展过程中，原癌基因表达的负调控持续中断，可能是由于肿瘤抑制基因的缺失。
Proliferation and proto-oncogene expression in 19 meningiomas of typical and atypical histology were analyzed in an attempt to understand the mechanism of growth that characterizes the neoplastic process in these tumors. Proliferation was estimated as the proliferative index by the enumeration of S-phase cells in imprints of tumor tissue exposed to bromodeoxyuridine in vitro, and the gene expression of c-myc, c-fos, c-src, c-H-ras, N-myc, acidic and basic fibroblast growth factor, insulin-like growth factors I and II, platelet-derived growth factor-alpha, and epidermal growth factor was quantified by messenger ribonucleic acid dot-blot hybridization assay. Atypical and malignant tumors had significantly higher proliferative indexes than did their nonmalignant counterparts. Levels of c-myc and c-fos messenger ribonucleic acid were elevated more than fivefold in 72 and 78% of the tumors, respectively, relative to the lowest levels detected in the series. Levels of growth factor messenger ribonucleic acid were sporadically elevated; 37 to 44% of tumors had more than fivefold enhanced levels of acidic and basic fibroblast growth factor. Positive correlations between proliferation and proto-oncogene/growth factor expression were found for c-myc in atypical/malignant tumors and for epidermal growth factor in fibroblastic meningiomas. Deregulated expression of c-myc and c-fos common to both typical and atypical tumors suggests that these are early events in the meningioma tumor process that may disturb the control of cell differentiation and together with fibroblast growth factors are likely to endow the transformed cell with a selective growth advantage by reducing the requirement for exogenous mitogens and by providing a niche for the growth of the tumor clone. Positive correlation of c-myc levels with proliferation in atypical/malignant meningiomas implies that this is a feature of malignancy and indicates continued disruption of the negative regulation of proto-oncogene expression, perhaps by tumor suppressor gene losses, during the course of tumor progression.