Holland E C, Li Y, Celestino J, Dai C, Schaefer L, Sawaya R A, Fuller G N
Department of Neurosurgery, Graduate Program in Genes and Development, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Am J Pathol. 2000 Sep;157(3):1031-7. doi: 10.1016/S0002-9440(10)64615-9.
The cells of origin for oligodendrogliomas and astrocytomas are not known but are presumed to be oligodendrocyte and astrocyte precursors, respectively. In this paper we report the generation of mixed gliomas from in vivo transformation of glial fibrillary acidic protein (GFAP)-positive cells (differentiated astrocytes) with polyoma virus middle T antigen (MTA). MTA is a powerful oncogene that activates a number of signal transduction pathways, including those proposed to be involved in gliomagenesis, and has been shown to induce tumors in many cell types. We have achieved transfer of MTA expression specifically to GFAP(+) cells in vivo using somatic cell gene transfer, and find resultant formation of anaplastic gliomas with mixed astrocytoma and oligodendroglioma morphological features. We conclude that GFAP- expressing astrocytes, with appropriate signaling abnormalities, can serve as the cell of origin for oligodendrogliomas, astrocytomas, or mixed gliomas.
少突胶质细胞瘤和星形细胞瘤的起源细胞尚不清楚，但推测分别为少突胶质细胞前体和星形胶质细胞前体。在本文中，我们报告了通过用多瘤病毒中T抗原（MTA）对胶质纤维酸性蛋白（GFAP）阳性细胞（分化的星形胶质细胞）进行体内转化而产生混合性胶质瘤。MTA是一种强大的致癌基因，可激活多种信号转导途径，包括那些被认为与胶质瘤发生有关的途径，并且已被证明能在许多细胞类型中诱导肿瘤。我们利用体细胞基因转移在体内实现了MTA表达特异性地转移到GFAP(+)细胞中，并发现形成了具有间变性胶质瘤以及混合性星形细胞瘤和少突胶质细胞瘤形态特征的肿瘤。我们得出结论，具有适当信号异常的表达GFAP的星形胶质细胞可作为少突胶质细胞瘤、星形细胞瘤或混合性胶质瘤的起源细胞。
