Katsetos Christos D, Dráberová Eduarda, Smejkalová Barbora, Reddy Goutham, Bertrand Louise, de Chadarévian Jean-Pierre, Legido Agustin, Nissanov Jonathan, Baas Peter W, Dráber Pavel
Department of Pediatrics, Drexel University College of Medicine and St. Christopher's Hospital for Children, Philadelphia, PA 19134, USA.
Neurochem Res. 2007 Aug;32(8):1387-98. doi: 10.1007/s11064-007-9321-1. Epub 2007 Apr 4.
We have previously shown that the neuronal-associated class III beta-tubulin isotype and the centrosome-associated gamma-tubulin are aberrantly expressed in astrocytic gliomas (Cell Motil Cytoskeleton 2003, 55:77-96; J Neuropathol Exp Neurol 2006, 65:455-467). Here we determined the expression, distribution and interaction of betaIII-tubulin and gamma-tubulin in diffuse-type astrocytic gliomas (grades II-IV) (n = 17) and the human glioblastoma cell line T98G. By immunohistochemistry and immunofluorescence microscopy, betaIII-tubulin and gamma-tubulin were co-distributed in anaplastic astrocytomas and glioblastomas and to a lesser extent, in low-grade diffuse astrocytomas (P < 0.05). In T98G glioblastoma cells betaIII-tubulin was associated with microtubules whereas gamma-tubulin exhibited striking diffuse cytoplasmic staining in addition to its expectant centrosome-associated pericentriolar distribution. Treatment with different anti-microtubule drugs revealed that betaIII-tubulin was not associated with insoluble gamma-tubulin aggregates. On the other hand, immunoprecipitation experiments unveiled that both tubulins formed complexes in soluble cytoplasmic pools, where substantial amounts of these proteins were located. We suggest that aberrant expression and interactions of betaIII-tubulin and gamma-tubulin may be linked to malignant changes in glial cells.
我们之前已经表明,神经元相关的III类β-微管蛋白异构体和中心体相关的γ-微管蛋白在星形胶质细胞瘤中异常表达(《细胞运动与细胞骨架》2003年,第55卷:77 - 96页;《神经病理学与实验神经病学杂志》2006年,第65卷:455 - 467页)。在此,我们确定了βIII-微管蛋白和γ-微管蛋白在弥漫型星形胶质细胞瘤(II - IV级)(n = 17)和人胶质母细胞瘤细胞系T98G中的表达、分布及相互作用。通过免疫组织化学和免疫荧光显微镜检查,βIII-微管蛋白和γ-微管蛋白在间变性星形细胞瘤和胶质母细胞瘤中共分布,在低级别弥漫性星形细胞瘤中分布较少(P < 0.05)。在T98G胶质母细胞瘤细胞中,βIII-微管蛋白与微管相关,而γ-微管蛋白除了预期的与中心体相关的中心粒周围分布外,还呈现出显著的弥漫性胞质染色。用不同的抗微管药物处理后发现,βIII-微管蛋白与不溶性γ-微管蛋白聚集体无关。另一方面,免疫沉淀实验表明,两种微管蛋白在可溶性胞质池中形成复合物,这些蛋白质大量存在于此。我们认为,βIII-微管蛋白和γ-微管蛋白的异常表达及相互作用可能与胶质细胞的恶性变化有关。