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低渗压力下基于突变型p53生物标志物驱动的转移性乳腺癌的阻抗检测

Impedimetric detection of mutant p53 biomarker-driven metastatic breast cancers under hyposmotic pressure.

作者信息

Shi Menglu, Shtraizent Nataly, Polotskaia Alla, Bargonetti Jill, Matsui Hiroshi

机构信息

Department of Chemistry, Hunter College and the Graduate Center, City University of New York, New York, New York, United States of America.

Department of Biological Sciences Hunter College and the Graduate Center, City University of New York, New York, New York, United States of America.

出版信息

PLoS One. 2014 Jun 17;9(6):e99351. doi: 10.1371/journal.pone.0099351. eCollection 2014.

Abstract

In cancer cells, the oncogenic mutant p53 (mtp53) protein is present at high levels and gain-of-function (GOF) activities with more expression of mtp53 proteins contribute to tumor growth and metastasis. Robust analytical approaches that probe the degree of metastasis of cancer cells in connection with the mtp53 activity will be extremely useful not only for establishing a better cancer prognosis but also understanding the fundamental mechanism of mtp53 oncogenic action. Here we assessed the influence of mtp53 in breast cancers to the mechanical property of breast cancer cells. Recently, ovarian and kidney cancer cell lines have been shown to have higher cellular elasticity as compared to normal cells assessed by monitoring the degree of deformation under hyposmotic pressure. To make fast detection in large scale, the impedance measurement was applied to monitor the swelling ratio of cells with time. The results showed that knockdown of mtp53 leads to decrease in cell swelling. In addition, by means of two types of impedimetric detection systems we consistently detected enhancement of impedance signal in mtp53-expressing breast cancer cells. Based on this observation we hypothesize that highly expressed mtp53 in metastatic mutant breast cancers can promote tumor progression by making cells more deformable and easier to spread out through extracellular matrix. The identification via the electric measurement can be accomplished within 10 minutes. All results in this report suggest that electric probing for the extent of the mtp53 expression of breast cancer cells may serve as a meaningful fingerprint for the cancer diagnostics, and this outcome will also have an important clinical implication for the development of mtp53-based targeting for tumor detection and treatment.

摘要

在癌细胞中,致癌突变型p53(mtp53)蛋白大量存在,mtp53蛋白表达量越高,其功能获得性(GOF)活性对肿瘤生长和转移的作用就越大。能够探究癌细胞转移程度与mtp53活性之间联系的强大分析方法,不仅对于建立更好的癌症预后评估体系极为有用,而且对于理解mtp53致癌作用的基本机制也非常重要。在此,我们评估了mtp53在乳腺癌中对乳腺癌细胞力学特性的影响。最近的研究表明,与通过监测低渗压力下的变形程度评估的正常细胞相比,卵巢和肾癌细胞系具有更高的细胞弹性。为了进行大规模的快速检测,采用阻抗测量来监测细胞随时间的肿胀率。结果表明,敲低mtp53会导致细胞肿胀减少。此外,通过两种阻抗检测系统,我们一致检测到表达mtp53的乳腺癌细胞中阻抗信号增强。基于这一观察结果,我们推测转移性突变乳腺癌中高表达的mtp53可通过使细胞更易变形并更容易通过细胞外基质扩散来促进肿瘤进展。通过电学测量进行鉴定可在10分钟内完成。本报告中的所有结果表明,对乳腺癌细胞mtp53表达程度进行电学探测可能作为癌症诊断的一个有意义的特征,这一结果对于基于mtp53的肿瘤检测和治疗靶点的开发也将具有重要的临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fe3/4060997/780e5b91aca2/pone.0099351.g001.jpg

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