Bögler O, Furnari F B, Kindler-Roehrborn A, Sykes V W, Yung R, Huang H J, Cavenee W K
Ludwig Institute for Cancer Research, University of California San Diego, La Jolla 92093-0660, USA.
Neuro Oncol. 2000 Jan;2(1):6-15. doi: 10.1093/neuonc/2.1.6.
Differential display polymerase chain reaction analysis was used to compare five differentiation states of the O-2A progenitor-like cell line CG4: progenitor cells and cells at 12 h or 4 days after the induction of differentiation into oligodendrocytes or astrocytes. This led to the identification of 52 sequence tags that were expressed differentially with cellular phenotype. One sequence was upregulated during differentiation of CG4 cells and represented a novel gene that we named SETA (SH3 domain-containing gene expressed in tumorigenic astrocytes). This gene encodes an SH3 domain-containing adapter protein with sequence similarity to the CD2AP (CD2 adapter protein) and CMS (Cas ligand with multiple Src homology) genes. SETA mRNA was expressed at high levels in the developing rat brain but was barely detectable in the normal adult rat or human brain. However, SETA mRNA was found in approximately one half of the human gliomas tested, including astrocytomas grades II, III, and IV, as well as oligodendrogliomas, mixed oligoastrocytomas, and human glioma-derived cell lines. A rat glioma generated by treatment with the alkylating carcinogen ethylnitrosourea on postnatal day 1 and a derived cell line also expressed SETA mRNA. Furthermore, in an in vitro model of astrocytoma progression based on p53-/- astrocytes, expression of SETA was restricted to cells that are tumorigenic.
差异显示聚合酶链反应分析用于比较O-2A祖细胞样细胞系CG4的五种分化状态：祖细胞以及诱导分化为少突胶质细胞或星形胶质细胞后12小时或4天的细胞。这导致鉴定出52个随细胞表型差异表达的序列标签。其中一个序列在CG4细胞分化过程中上调，代表一个新基因，我们将其命名为SETA（在致瘤性星形胶质细胞中表达的含SH3结构域的基因）。该基因编码一种含SH3结构域的衔接蛋白，其序列与CD2AP（CD2衔接蛋白）和CMS（具有多个Src同源性的Cas配体）基因相似。SETA mRNA在发育中的大鼠脑中高水平表达，但在正常成年大鼠或人脑中几乎检测不到。然而，在所检测的大约一半人类胶质瘤中发现了SETA mRNA，包括II级、III级和IV级星形细胞瘤，以及少突胶质细胞瘤、混合性少突星形细胞瘤和人胶质瘤衍生细胞系。出生后第1天用烷基化致癌物乙基亚硝基脲处理产生的大鼠胶质瘤及其衍生细胞系也表达SETA mRNA。此外，在基于p53基因敲除星形胶质细胞的星形细胞瘤进展体外模型中，SETA的表达仅限于具有致瘤性的细胞。
