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Expression of the stress-associated protein p8 is a requisite for tumor development.

机译:压力相关蛋白p8的表达是肿瘤发展的必要条件。

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摘要

We identified a new gene, called p8, because its expression was strongly induced during the acute phase of pancreatitis. Further experiments have shown that p8 mRNA is activated in response to several stresses and that its activation is not restricted to pancreatic cells. p8 is a nuclear protein and biochemical and biophysical studies have shown that p8 was very similar in many structural aspects to the HMG proteins, although sharing only low amino acid sequence homology. Also, p8 was found overexpressed in many human cancers. Therefore, we wondered whether the p8-mediated response to cellular stress was necessary for tumor establishment. Subcutaneous or intraperitoneal injections of transformed p8-expressing fibroblasts led to tumor formation in nude mice, but no tumor was observed with transformed p8-deficient cells. Restoring p8 expression in transformed p8-deficient fibroblasts led to tumor formation, demonstrating that p8 expression is crucial for tumor development and suggesting that the stress-response mechanisms governed by p8 are required for tumor establishment.
机译:我们鉴定了一个称为p8的新基因,因为其表达在胰腺炎的急性期被强烈诱导。进一步的实验表明,p8 mRNA可响应多种压力而被激活,并且其激活并不局限于胰腺细胞。 p8是一种核蛋白,生化和生物物理研究表明,p8在许多结构方面与HMG蛋白非常相似,尽管仅具有低氨基酸序列同源性。而且,在许多人类癌症中发现p8过表达。因此,我们想知道p8介导的对细胞应激的反应对于肿瘤的建立是否必要。皮下或腹膜内注射表达p8的转化成纤维细胞导致裸鼠中肿瘤形成,但用转化的p8缺陷细胞未观察到肿瘤。在转化的缺乏p8的成纤维细胞中恢复p8的表达会导致肿瘤的形成,这表明p8的表达对于肿瘤的发展至关重要,这表明建立肿瘤需要p8调控的应激反应机制。

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