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相关概念视频

Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

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Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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Updated: Sep 10, 2025

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions
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暴露于缺氧的肌肉侵入性和非肌肉侵入性膀癌细胞中的基因表达

Rekaya Shabbir1, Conrado G Quiles1, Brian Lane1

  • 1Division of Cancer Sciences, University of Manchester, Manchester M20 4GJ, UK.

Cancers
|August 28, 2025
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概括

在低氧性膀癌中研究基因表达, 这一发现对于开发用于抗辐射癌症疾病进展和预后的新生物标志物至关重要.

关键词:
膀癌症没有氧气标志性生物标志物转录组

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科学领域:

  • 癌症学
  • 分子生物学
  • 基因组学

背景情况:

  • 低氧瘤具有抗辐射性,因此需要生物标志物来指导低氧向治疗.
  • 目前的生物标志物通常依赖于暴露在1%氧气中的细胞的基因表达数据,在较低,更异质的瘤氧气水平 (<0.1%) 中可能缺失反应.

研究的目的:

  • 研究不同氧度 (0.1%,0.2%,1%,20%) 如何影响膀癌细胞系的基因表达.
  • 在较低的氧气水平下识别的基因特征的预后能力与现有的特征进行比较.
  • 确定新型低氧反应基因和与膀癌侵袭性和预后相关的途径.

主要方法:

  • 四种肌肉侵入性膀癌 (MIBC) 和两种非MIBC细胞系在24小时内暴露在不同水平的氧气中.
  • 使用Clariom S微阵列分析转录组以识别差异表达的基因.
  • 将已发表的24个基因特征与来自低氧识别基因的新特征的预后和预测意义进行了比较.

主要成果:

  • 随着氧气水平的下降, 上调基因和相关生物通路的数量增加.
  • 在0.1%的氧气中,至少有3个细胞系的77个基因被上调.
  • 来自低氧反应基因的5基因特征显示出与24基因特征相似的预后,但没有预测治疗益处.

结论:

  • 膀癌中对缺氧的基因表达反应取决于氧度,在较低的氧度下,更多的基因被上调.
  • 在低氧状态下,MIBC和NMIBC细胞之间的基因表达差异为膀癌的侵入性提供了洞察力.
  • 这项研究是首次评估膀癌多种低氧基因表达,以确定新的预后生物标志物.