Detta A, Kenny B G, Smith C, Logan A, Hitchcock E
Department of Neurosurgery, University of Birmingham, England.
Neurosurgery. 1993 Dec;33(6):1065-74. doi: 10.1227/00006123-199312000-00015.
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.
对19例具有典型和非典型组织学特征的脑膜瘤的增殖和原癌基因表达进行了分析，旨在了解这些肿瘤中肿瘤形成过程的生长机制。通过体外暴露于溴脱氧尿苷的肿瘤组织印记中S期细胞的计数，将增殖作为增殖指数进行估计，并通过信使核糖核酸斑点杂交试验对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、血小板衍生生长因子-α以及表皮生长因子的基因表达进行定量。非典型和恶性肿瘤的增殖指数显著高于其非恶性对应物。相对于该系列中检测到的最低水平，c-myc和c-fos信使核糖核酸水平分别在72%和78%的肿瘤中升高了五倍以上。生长因子信使核糖核酸水平偶尔升高；37%至44%的肿瘤酸性和碱性成纤维细胞生长因子水平增强了五倍以上。在非典型/恶性肿瘤中，c-myc的增殖与原癌基因/生长因子表达之间存在正相关，在纤维母细胞性脑膜瘤中，表皮生长因子也存在正相关。典型和非典型肿瘤中共同存在的c-myc和c-fos表达失调表明，这些是脑膜瘤肿瘤形成过程中的早期事件，可能会干扰细胞分化的控制，并且与成纤维细胞生长因子一起，可能通过减少对外源性有丝分裂原的需求并为肿瘤克隆的生长提供生态位，赋予转化细胞选择性生长优势。非典型/恶性脑膜瘤中c-myc水平与增殖的正相关意味着这是恶性肿瘤的一个特征，并表明在肿瘤进展过程中，原癌基因表达的负调控可能因肿瘤抑制基因的缺失而持续受到破坏。
