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首页> 外文期刊>Journal of Cellular Physiology >Progression elevated gene-3, PEG-3, induces genomic instability in rodent and human tumor cells.
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Progression elevated gene-3, PEG-3, induces genomic instability in rodent and human tumor cells.

机译：发展基因3升高,PEG-3,诱发基因组不稳定性在啮齿动物和人类肿瘤细胞。

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摘要

Genomic instability is a fundamental component of cancer progression. Subtraction hybridization identified a novel rodent gene, progression elevated gene-3 (PEG-3) whose expression directly correlates with cancer aggressiveness and progression. Moreover, ectopic expression of PEG-3 in rodent or human tumor cells produces an aggressive transformed phenotype. We demonstrate that PEG-3 expression in rodent tumor cells correlates directly with genomic instability as characterized by alterations in chromosome composition and structure. Additionally, elevated endogenous or ectopic expression of PEG-3 in rodent and human tumor cells, respectively, enhances gene amplification, as monitored by resistance to methothrexate (MTX) and amplification of the dihydrofolate reductase (dhfr) gene. Stable expression of PEG-3 in normal cloned rat embryo fibroblast (CREF) cells marginally elevates MTX resistance, but morphology remains unaltered and anchorage independence is not induced, suggesting that these phenotypes are separable in immortal cells and gene amplification may precede the acquisition of morphological and oncogenic transformation. The present studies document that stable, inducible, and transient expression of PEG-3 in cancer cells augments genomic instability. In these contexts, one mechanism by which PEG-3 influences cancer progression may be by preferentially facilitating the development of genomic changes in evolving cancer cells.
机译：基因组不稳定性是一个基本组成部分癌症的发展。发现了一个新奇的啮齿动物基因,进展基因3 (PEG-3)升高的直接表达与癌症侵犯进展。PEG-3啮齿动物或人类肿瘤细胞产生积极的转化表型。在啮齿动物肿瘤细胞PEG-3表达式与基因组不稳定性直接相关以改变染色体组成和结构。内源性或PEG-3的异位表达啮齿动物和人类的肿瘤细胞,分别提高基因扩增,所监控的抵抗methothrexate (MTX)和二氢叶酸还原酶的放大(dhfr)基因。克隆鼠胚胎成纤维细胞(CREF)细胞略微提升MTX耐药,但是形态依然没有改变,安克雷奇独立并不是诱导,这表明在不朽内存中这些表型分离细胞和基因扩增可能之前收购的形态和致癌转换。稳定、诱导和瞬态的表达PEG-3增强基因在癌症细胞不稳定。PEG-3影响癌症恶化可能是哪一个通过优先促进的发展基因组进化癌细胞的变化。

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