Global gene expression profiling in three tumor cell lines subjected to experimental cycling and chronic hypoxia.
Global gene expression profiling in three tumor cell lines subjected to experimental cycling and chronic hypoxia.
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DOI：
10.1371/journal.pone.0105104
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Lisowska KM
中科院分区：
文献类型：
--
作者：
Olbryt M;Habryka A;Student S;Jarząb M;Tyszkiewicz T;Lisowska KM
缺氧是肿瘤微环境最重要的特征之一，对肿瘤的侵袭性和患者预后产生不利影响。在肿瘤块内可能发生两种类型的缺氧，慢性（长期）和循环（短暂的，间歇性）缺氧。循环性缺氧比慢性缺氧更能诱导肿瘤细胞的侵袭性表型和放射抗性，但目前对这一现象的分子机制知之甚少。本研究的目的是描绘的分子反应，以两种类型的缺氧诱导实验肿瘤细胞，重点是循环缺氧。我们分析了暴露于实验性慢性或短暂缺氧条件下的三种人类癌细胞系（黑色素瘤、卵巢癌和前列腺癌）的体外基因表达谱。正如预期的那样，响应于缺氧的细胞类型特异性变异性是显著的。然而，240个探针组的表达在所有3个细胞系中改变。我们发现，这两种类型的缺氧诱导的基因表达谱是定性相似的，强烈依赖于细胞类型。与慢性缺氧相比，循环缺氧改变较少基因的表达（6，132对8，635探针组，FDR调整的p<0.05），并且具有较低的倍数变化。然而，这些基因中的一些基因的表达受循环缺氧的影响比长时间缺氧的影响更大，如IL 8，PLAU和表皮生长因子（EGF）通路相关基因（AREG，HBEGF和EPHA 2）。在大多数情况下，这些成绩单，验证定量逆转录聚合酶链反应（qRT-PCR）。我们的研究结果表明，实验性循环缺氧产生类似的，虽然不太强烈的影响，检查癌细胞系比其慢性对应。尽管如此，我们确定的基因和分子途径，似乎优先调节循环缺氧。
Hypoxia is one of the most important features of the tumor microenvironment, exerting an adverse effect on tumor aggressiveness and patient prognosis. Two types of hypoxia may occur within the tumor mass, chronic (prolonged) and cycling (transient, intermittent) hypoxia. Cycling hypoxia has been shown to induce aggressive tumor cell phenotype and radioresistance more significantly than chronic hypoxia, though little is known about the molecular mechanisms underlying this phenomenon. The aim of this study was to delineate the molecular response to both types of hypoxia induced experimentally in tumor cells, with a focus on cycling hypoxia. We analyzed in vitro gene expression profile in three human cancer cell lines (melanoma, ovarian cancer, and prostate cancer) exposed to experimental chronic or transient hypoxia conditions. As expected, the cell-type specific variability in response to hypoxia was significant. However, the expression of 240 probe sets was altered in all 3 cell lines. We found that gene expression profiles induced by both types of hypoxia were qualitatively similar and strongly depend on the cell type. Cycling hypoxia altered the expression of fewer genes than chronic hypoxia (6,132 vs. 8,635 probe sets, FDR adjusted p<0.05), and with lower fold changes. However, the expression of some of these genes was significantly more affected by cycling hypoxia than by prolonged hypoxia, such as IL8, PLAU, and epidermal growth factor (EGF) pathway-related genes (AREG, HBEGF, and EPHA2). These transcripts were, in most cases, validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Our results indicate that experimental cycling hypoxia exerts similar, although less intense effects, on the examined cancer cell lines than its chronic counterpart. Nonetheless, we identified genes and molecular pathways that seem to be preferentially regulated by cyclic hypoxia.
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影响因子：
14.9
作者：
Benita Y;Kikuchi H;Smith AD;Zhang MQ;Chung DC;Xavier RJ
通讯作者：
Xavier RJ
影响因子：
10.3
作者：
Lal, A;Peters, H;Riggins, GJ
通讯作者：
Riggins, GJ
影响因子：
2.6
作者：
BROWN, JM
通讯作者：
BROWN, JM
影响因子：
5.7
作者：
Brurberg, KG;Skogmo, HK;Rofstad, EK
通讯作者：
Rofstad, EK
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y