Murphy M, Pykett M J, Harnish P, Zang K D, George D L
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104-6145.
Cell Growth Differ. 1993 Sep;4(9):715-22.
Meningiomas are common tumours derived from the thin membrane that surrounds the brain and spinal cord. Currently, the molecular mechanisms responsible for the initiation and progression of these tumors are largely unknown. Toward the elucidation of such mechanisms, we have formulated an experimental design utilizing the technique of subtractive hybridization that is aimed at identifying the changes in gene expression between intracranial meningiomas and their normal precursor cells, leptomeningeal cells. We report here the identification and initial characterization of three genes whose expression is altered or aberrant in meningioma cell lines and tumours relative to cultures of normal leptomeningeal cells. Complementary DNA probes from one of these genes detect transcripts of altered size in several meningiomas relative to normal leptomeningeal cells. Another of these genes demonstrates decreased expression in meningiomas and in tumours associated with the disorder neurofibromatosis 2. A third gene isolated by this procedure is differentially expressed in both meningiomas and breast carcinomas. Therefore, the decreased expression of these genes may play roles in growth-regulatory pathways that are abrogated not only in meningiomas, but in other tumor types as well.
脑膜瘤是源自围绕脑和脊髓的薄膜的常见肿瘤。目前,这些肿瘤发生和进展的分子机制在很大程度上尚不清楚。为了阐明这些机制,我们制定了一种实验设计,利用消减杂交技术,旨在识别颅内脑膜瘤与其正常前体细胞(软脑膜细胞)之间基因表达的变化。我们在此报告了三个基因的鉴定和初步表征,这些基因在脑膜瘤细胞系和肿瘤中的表达相对于正常软脑膜细胞培养物发生了改变或异常。来自其中一个基因的互补DNA探针检测到相对于正常软脑膜细胞,在几个脑膜瘤中大小改变的转录本。这些基因中的另一个在脑膜瘤和与2型神经纤维瘤病相关的肿瘤中表达降低。通过该程序分离的第三个基因在脑膜瘤和乳腺癌中均有差异表达。因此,这些基因表达的降低可能在生长调节途径中起作用,这些途径不仅在脑膜瘤中被废除,在其他肿瘤类型中也是如此。