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首页> 外文期刊>Cell cycle >Entrainment of breast (cancer) epithelial cells detects distinct circadian oscillation patterns for clock and hormone receptor genes
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Entrainment of breast (cancer) epithelial cells detects distinct circadian oscillation patterns for clock and hormone receptor genes

机译：乳腺癌（癌）上皮细胞的夹带检测出时钟和激素受体基因的不同昼夜节律振荡模式

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Most physiological and biological processes are regulated by endogenous circadian rhythms under the control of both a master clock, which acts systemically and individual cellular clocks, which act at the single cell level. The cellular clock is based on a network of core clock genes, which drive the circadian expression of non-clock genes involved in many cellular processes. Circadian deregulation of gene expression has emerged to be as important as deregulation of estrogen signaling in breast tumorigenesis. Whether there is a mutual deregulation of circadian and hormone signaling is the question that we address in this study. Here we show that, upon entrainment by serum shock, cultured human mammary epithelial cells maintain an inner circadian oscillator, with key clock genes oscillating in a circadian fashion. In the same cells, the expression of the estrogen receptor α (ERA) gene also oscillates in a circadian fashion. In contrast, ER A-positive and -negative breast cancer epithelial cells show disruption of the inner clock. Further, ER A-positive breast cancer cells do not display circadian oscillation of ERA expression. Our findings suggest that estrogen signaling could be affected not only in ER A-negative breast cancer, but also in ER A-positive breast cancer due to lack of circadian availability of ER A. Entrainment of the inner clock of breast epithelial cells, by taking into consideration the biological time component, provides a novel tool to test mechanistically whether defective circadian mechanisms can affect hormone signaling relevant to breast cancer.
机译：大多数生理和生物学过程均受内源性昼夜节律的调节，这些节律在系统作用的主时钟和作用于单个细胞水平的单个细胞时钟的控制下进行。细胞时钟基于核心时钟基因的网络，该基因驱动许多细胞过程中涉及的非时钟基因的昼夜表达。昼夜节律性基因表达的失调与乳腺肿瘤发生中雌激素信号转导的失调一样重要。昼夜节律和激素信号是否相互放松是我们在这项研究中要解决的问题。在这里，我们显示，在受到血清休克的刺激后，培养的人乳腺上皮细胞保持了一个内部昼夜节律振荡器，其中关键时钟基因以昼夜节律振荡。在同一细胞中，雌激素受体α（ERA）基因的表达也以昼夜节律的方式振荡。相反，ER A阳性和阴性乳腺癌上皮细胞显示内部时钟被破坏。此外，ER A阳性乳腺癌细胞不显示ERA表达的昼夜节律振荡。我们的研究结果表明，雌激素信号传导不仅可能在ER A阴性乳腺癌中受到影响，而且由于缺乏ER A的昼夜可利用性，也可能在ER A阳性乳腺癌中受到影响。通过摄取乳腺上皮细胞的内时钟考虑到生物学上的时间成分，提供了一种新颖的工具来机械地检测生物节律机制是否会影响与乳腺癌有关的激素信号传导。

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