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首页> 外文期刊>Molecular and Cellular Biology >Reversible Tumorigenesis Induced by Deficiency of Vasodilator-Stimulated Phosphoprotein
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Reversible Tumorigenesis Induced by Deficiency of Vasodilator-Stimulated Phosphoprotein

机译：血管扩张剂刺激的磷酸蛋白缺乏引起的可逆的肿瘤发生

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Random homozygous knockout (RHKO) is an antisense RNA strategy capable of identifying genes whose homozygous functional inactivation yields a selectable phenotype in cells growing in culture. Using this approach, we isolated NIH 3T3 fibroblast clones that showed the ability to form colonies on 0.5% agar and tumors in nude mice. The gene inactivated in one of these clones was found to encode VASP (vasodilator-stimulated phosphoprotein), a previously identified protein that binds to components of the cadherin-catenin junctional complex and has been implicated in cell-cell interactions, the formation of actin filaments, and the transmission of signals at the cytoskeleton-membrane interface. Fibroblasts made deficient in VASP by RHKO showed loss of contact inhibition, and consequently, continued cell division past confluence. Restoration of VASP function by reversal of RHKO yielded cells that had lost the neoplastic capabilities acquired during RHKO. Overproduction of VASP mRNA in the sense or antisense orientation from expression constructs introduced by transfection into naive NIH 3T3 fibroblasts also resulted in neoplastic transformation, implying that normal cell growth may require the maintenance of VASP expression within a narrow range. Our results implicate VASP in tumorigenesis and/or cancer progression.
机译：随机纯合敲除（RHKO）是一种反义RNA策略，能够识别其纯合功能失活在培养的细胞中产生可选择表型的基因。使用这种方法，我们分离了NIH 3T3成纤维细胞克隆，该克隆显示出在裸鼠中0.5％琼脂和肿瘤上形成集落的能力。发现在这些克隆之一中失活的基因编码VASP（血管扩张剂刺激的磷蛋白），该蛋白是先前鉴定的蛋白，与钙粘蛋白-连环蛋白连接复合物的成分结合，并参与细胞-细胞相互作用，肌动蛋白丝的形成。 ，以及在细胞骨架-膜界面的信号传输。 RHKO使VASP缺乏的成纤维细胞失去了接触抑制作用，因此经过融合后继续进行细胞分裂。通过逆转RHKO恢复VASP功能产生的细胞失去了在RHKO期间获得的赘生能力。通过转染至幼稚的NIH 3T3成纤维细胞中的表达构建体，有义或反义方向VASP mRNA的过量生产也会导致肿瘤转化，这意味着正常细胞的生长可能需要将VASP表达维持在狭窄的范围内。我们的结果表明VASP参与了肿瘤的发生和/或癌症的发展。

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