Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA 90048, USA.
Integr Cancer Ther. 2009 Dec;8(4):317-20. doi: 10.1177/1534735409352084. Epub 2009 Nov 18.
Circadian rhythms are endogenous biological clocks that govern fundamental physiological and behavioral functions. Consequently, perturbations of these rhythms have been associated with pathogenic conditions, such as depression, diabetes, and cancer. CCAAT/enhancer-binding proteins (C/EBPs) are a family of transcription factors that regulate cell growth and differentiation in various tissues and have also been implicated in many cancer types. Using expression profiling studies, we found that the levels of 2 core components of the circadian network, Per2 and Rev-Erb alpha, are significantly altered by C/EBPs. Further studies showed that levels of Per2 were reduced in lymphoma and acute myeloid leukemia patient samples, as well as in lymphoma cell lines. Overexpression of Per2 in hematopoietic cancer cell lines resulted in growth inhibition, cell cycle arrest, apoptosis and loss of clonogenic ability. These results support the emerging role of circadian genes in tumor suppression.
昼夜节律是内在的生物钟，控制着基本的生理和行为功能。因此，这些节律的紊乱与发病条件有关，如抑郁症、糖尿病和癌症。CCAAT/增强子结合蛋白（C/EBP）是一类转录因子，可调节各种组织中的细胞生长和分化，也与许多癌症类型有关。通过表达谱研究，我们发现昼夜节律网络的 2 个核心组成部分，Per2 和 Rev-Erb alpha，的水平受到 C/EBP 的显著改变。进一步的研究表明，淋巴瘤和急性髓细胞白血病患者样本以及淋巴瘤细胞系中 Per2 的水平降低。在造血癌细胞系中过表达 Per2 会导致生长抑制、细胞周期停滞、凋亡和丧失克隆形成能力。这些结果支持昼夜节律基因在肿瘤抑制中的作用正在不断发展。
