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首页> 外文期刊>Cell Division >Real-time in vivo imaging of p16Ink4a gene expression: a new approach to study senescence stress signaling in living animals
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Real-time in vivo imaging of p16Ink4a gene expression: a new approach to study senescence stress signaling in living animals

机译：p16Ink4a基因表达的实时体内成像：研究活体动物衰老应激信号的新方法

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摘要

Oncogenic proliferative signals are coupled to a variety of growth inhibitory processes. In cultured primary human fibroblasts, for example, ectopic expression of oncogenic Ras or its downstream mediator initiates cellular senescence, the state of irreversible cell cycle arrest, through up-regulation of cyclin-dependent kinase (CDK) inhibitors, such as p16INK4a. To date, much of our current knowledge of how human p16INK4a gene expression is induced by oncogenic stimuli derives from studies undertaken in cultured primary cells. However, since human p16INK4a gene expression is also induced by tissue culture-imposed stress, it remains unclear whether the induction of human p16INK4a gene expression in tissue-cultured cells truly reflects an anti-cancer process or is an artifact of tissue culture-imposed stress. To eliminate any potential problems arising from tissue culture imposed stress, we have recently developed a bioluminescence imaging (BLI) system for non-invasive and real-time analysis of human p16INK4a gene expression in the context of a living animal. Here, we discuss the molecular mechanisms that direct p16INK4a gene expression in vivo and its potential for tumor suppression.
机译：致癌性增殖信号与多种生长抑制过程相关。例如，在培养的原始人类成纤维细胞中，致癌性Ras或其下游介体的异位表达通过上调细胞周期蛋白依赖性激酶（CDK）抑制剂（例如p16 ）来启动细胞衰老，不可逆细胞周期停滞状态。 INK4a 。迄今为止，我们对致癌刺激如何诱导人p16 INK4a 基因表达的许多了解，都来自在培养的原代细胞中进行的研究。然而，由于人p16 INK4a 基因的表达也受到组织培养施加的压力的诱导，因此尚不清楚组织培养细胞中人p16 INK4a 基因表达的诱导是否真正反映抗癌过程或是组织培养物施加的压力的假象。为了消除由于组织培养施加的压力而引起的任何潜在问题，我们最近开发了一种生物发光成像（BLI）系统，用于在人体内p16 INK4a 基因表达的非侵入性实时分析中活体动物。在这里，我们讨论了指导p16 INK4a 基因在体内表达的分子机制及其抑制肿瘤的潜力。

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