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首页> 外文期刊>Electrophoresis: The Official Journal of the International Electrophoresis Society >PROTEIN EXPRESSION CHANGES ASSOCIATED WITH RADIATION-INDUCED NEOPLASTIC PROGRESSION OF HUMAN PROSTATE EPITHELIAL CELLS
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PROTEIN EXPRESSION CHANGES ASSOCIATED WITH RADIATION-INDUCED NEOPLASTIC PROGRESSION OF HUMAN PROSTATE EPITHELIAL CELLS

机译:辐射诱导人前列腺上皮细胞蛋白表达与蛋白质表达的变化

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Carcinogenic progression in most epithelial systems is a multistep process and presents as numerous (un)stable intermediate stages prior to the development of a fully malignant phenotype. Recently, we reported the neoplastic transformation of an SV40 immortalized, neonatal human prostate epithelial cell line (267B1) by multiple exposures to X-rays [1, 2]. The parental 267B1 cells acquired anchorage-independence and exhibited morphological transformation following exposure to two consecutive doses of 2 Gy. Exposure of either the parental 267B1 cells or the anchorage-independent derivatives (F3-SAC) to a total dose of 30 Gy of X-rays yielded tumorigenic transformants (267B1-XR and 267B1-SXR, respectively). All of these radiation-treated derivatives (F3-SAC, 267B1-XR, and 267B1-SXR) were characterized by reduced cell size and poorly organized actin stress fibers [2, 3]. The present study examines the protein expression changes associated with cytoskeletal alterations during the different steps of neoplastic progression induced by X-rays in the in vitro human prostate cell system. This analysis was achieved by using the high resolving power of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) in the 267B1, F3-SAC, 267B1-XR, and 267B1-SXR cells. We report changes in the expression of gelsolin in the partially transformed, anchorage-independent, nontumorigenic (F3-SAC) cells and a progressive loss of expression of tropomyosin isoforms (TM-1 and TM-3), and myosin light chain-2 (MLC-2) in the tumorigenic (267B1-XR; 267B1-SXR) cells, respectively. In contrast, our results demonstrate that the levels of the small GTP-binding protein Rho-A, an active participant in the actin stress fiber organization, are not altered during neoplastic progression of these 267B1 cells. Thus the changes in synthesis of gelsolin, tropomyosins, and MLC-2 provide a rationale for the alterations in the actin stress fiber formation and reduction in cell size during the exposure of prostate epithelial cells to multiple doses of X-rays. [References: 40]
机译:在大多数上皮系统中,致癌性进展是一个多步骤过程,在完全恶性表型发展之前,表现为许多(不稳定)的中间阶段。最近,我们报道了通过多次暴露于X射线对SV40永生化的新生儿人前列腺上皮细胞系(267B1)进行的肿瘤转化[1,2]。亲本267B1细胞获得了锚固独立性并暴露于两个连续剂量的2 Gy后表现出形态转化。将亲本267B1细胞或独立于锚定的衍生物(F3-SAC)暴露于总剂量为30 Gy的X射线,即可产生致瘤性转化子(分别为267B1-XR和267B1-SXR)。所有这些经过辐射处理的衍生物(F3-SAC,267B1-XR和267B1-SXR)的特征是细胞尺寸减小和肌动蛋白应力纤维组织不良[2,3]。本研究检查了在体外人前列腺细胞系统中X射线诱导的肿瘤进展不同步骤中与细胞骨架改变有关的蛋白质表达变化。通过在267B1,F3-SAC,267B1-XR和267B1-SXR细胞中使用二维聚丙烯酰胺凝胶电泳(2-D PAGE)具有较高的分辨能力,可以完成此分析。我们报告了凝溶胶蛋白在部分转化,不依赖锚固,非致瘤性(F3-SAC)的细胞中表达的变化以及原肌球蛋白同工型(TM-1和TM-3)和肌球蛋白轻链2( MLC-2)分别位于致瘤性(267B1-XR; 267B1-SXR)细胞中。相反,我们的结果表明,在这些267B1细胞的肿瘤进展过程中,肌动蛋白应激纤维组织的积极参与者小GTP结合蛋白Rho-A的水平没有改变。因此,凝溶胶蛋白,原肌球蛋白和MLC-2的合成变化为在前列腺上皮细胞暴露于多次剂量的X射线期间肌动蛋白应激纤维形成的改变和细胞大小的减少提供了理论依据。 [参考:40]

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