Clock Cell Biology Group, Institute for Biological Resource and Function, National Institute of Advanced Industrial Science and Technology, Tsukuba Central 6, 1-1-1, Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Genes Cells. 2010 Apr 1;15(4):351-8. doi: 10.1111/j.1365-2443.2010.01384.x. Epub 2010 Mar 4.
Some reports have indicated that the core clock gene, Per2 regulates the cell cycle, immune system and neural functions. To understand the effects of PER2 on tumor growth in vivo, stable transformants of murine sarcoma 180 (S-180) cell lines expressing different levels of PER2 were established. The growth of stable PER2 transformants in vivo was significantly and dose-dependently suppressed according to the amount of PER2 expressed, indicating that PER2 plays a role in the growth suppression of sarcoma cells. The anchorage-dependent and -independent growth in vitro and expression of the clock controlled cell-cycle related genes, wee1, myc, and VEGF were not altered in stable PER2 transformants. In contrast, susceptibility to murine natural killer (NK) cell cytolytic activity was enhanced in PER2 transformants. Furthermore, PER2 transformants suppressed cell motility and reduced fibronectin expression, but the expression of integrin receptors was not affected. These results suggest that sarcoma cells overexpressing PER2 suppress tumors in vivo by changing the nature of tumor cell adhesion.
一些报告表明，核心时钟基因 PER2 调节细胞周期、免疫系统和神经功能。为了了解 PER2 对体内肿瘤生长的影响，建立了表达不同水平 PER2 的鼠肉瘤 180（S-180）细胞系的稳定转染体。根据表达的 PER2 量，稳定 PER2 转染体在体内的生长明显呈剂量依赖性抑制，表明 PER2 在肉瘤细胞生长抑制中发挥作用。体外的锚定依赖性和非依赖性生长以及时钟控制的细胞周期相关基因 wee1、myc 和 VEGF 的表达在稳定 PER2 转染体中没有改变。相比之下，PER2 转染体增强了对鼠自然杀伤（NK）细胞细胞溶解活性的敏感性。此外，PER2 转染体抑制细胞迁移并降低纤连蛋白表达，但整合素受体的表达不受影响。这些结果表明，过表达 PER2 的肉瘤细胞通过改变肿瘤细胞黏附的性质在体内抑制肿瘤。
