对暴露于缺氧环境的恶性黑色素瘤细胞系的分析揭示了过表达对疾病进展的重要性。
Analysis of Malignant Melanoma Cell Lines Exposed to Hypoxia Reveals the Importance of Overexpression for Disease Progression.
作者信息
Trojan Sonia E, Piwowar Monika, Ostrowska Barbara, Laidler Piotr, Kocemba-Pilarczyk Kinga A
机构信息
Chair of Medical Biochemistry, Faculty of Medicine, Jagiellonian University - Medical College, Cracow, Poland.
Department of Bioinformatics and Telemedicine, Faculty of Medicine, Jagiellonian University - Medical College, Cracow, Poland.
出版信息
Anticancer Res. 2018 Dec;38(12):6745-6752. doi: 10.21873/anticanres.13044.
BACKGROUND/AIM: Most melanomas develop in hypoxic conditions. Since hypoxia via HIF-1 induces glycolysis, a process essential for malignant melanoma growth/survival, the goal of this study was to analyze the influence of hypoxia on the expression of HIF-1 target genes involved in glucose metabolism.
MATERIALS AND METHODS
The response of melanoma cell lines to hypoxic conditions was analyzed by RT-PCR and western blotting. A Kaplan-Meier survival analysis for patients with high and low expression level of PFKFB4 was performed. Further analysis of patients' data was performed using the R/Bioconductor environment.
RESULTS
Induction of PFKFB4 gene expression can be considered a crucial mechanism behind glycolysis enhancement in hypoxic melanoma cells. Analysis of a publicly available database revealed that high PFKFB4 expression contributes to poor prognosis of melanoma patients.
CONCLUSION
Currently available anti-melanoma therapeutic strategies may significantly benefit from agents targeting PFKFB4 activity.
背景/目的：大多数黑色素瘤在缺氧条件下发生。由于缺氧通过缺氧诱导因子-1（HIF-1）诱导糖酵解，而糖酵解是恶性黑色素瘤生长/存活所必需的过程，本研究的目的是分析缺氧对参与葡萄糖代谢的HIF-1靶基因表达的影响。
材料与方法
通过逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法分析黑色素瘤细胞系对缺氧条件的反应。对磷酸果糖激酶-2/果糖-2,6-二磷酸酶4（PFKFB4）高表达和低表达水平的患者进行Kaplan-Meier生存分析。使用R/Bioconductor环境对患者数据进行进一步分析。
结果
PFKFB4基因表达的诱导可被认为是缺氧黑色素瘤细胞中糖酵解增强背后的关键机制。对一个公开可用数据库的分析表明，PFKFB4高表达导致黑色素瘤患者预后不良。
结论
目前可用的抗黑色素瘤治疗策略可能会从靶向PFKFB4活性的药物中显著获益。
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