Xiang Shulin, Coffelt Seth B, Mao Lulu, Yuan Lin, Cheng Qi, Hill Steven M
Department of Structural and Cellular Biology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
J Circadian Rhythms. 2008 Mar 11;6:4. doi: 10.1186/1740-3391-6-4.
Previous reports have suggested that the ablation of the Period 2 gene (Per 2) leads to enhanced development of lymphoma and leukemia in mice. Employing immunoblot analyses, we have demonstrated that PER 2 is endogenously expressed in human breast epithelial cell lines but is not expressed or is expressed at significantly reduced level in human breast cancer cell lines. Expression of PER 2 in MCF-7 breast cancer cells significantly inhibited the growth of MCF-7 human breast cancer cells, and, when PER 2 was co-expressed with the Crytochrome 2 (Cry 2) gene, an even greater growth-inhibitory effect was observed. The inhibitory effect of PER 2 on breast cancer cells was also demonstrated by its suppression of the anchorage-independent growth of MCF-7 cells as evidenced by the reduced number and size of colonies. A corresponding blockade of MCF-7 cells in the G1 phase of the cell cycle was also observed in response to the expression of PER 2 alone or in combination with CRY 2. Expression of PER 2 also induced apoptosis of MCF-7 breast cancer cells as demonstrated by an increase in PARP [poly (ADP-ribose) polymerase] cleavage. Finally, our studies demonstrate that PER 2 expression in MCF-7 breast cancer cells is associated with a significant decrease in the expression of cyclin D1 and an up-regulation of p53 levels.
先前的报道表明，Period 2基因（Per 2）的缺失会导致小鼠淋巴瘤和白血病的发展加剧。通过免疫印迹分析，我们证明PER 2在人乳腺上皮细胞系中内源性表达，但在人乳腺癌细胞系中不表达或表达水平显著降低。PER 2在MCF-7乳腺癌细胞中的表达显著抑制了MCF-7人乳腺癌细胞的生长，并且，当PER 2与细胞色素2（Cry 2）基因共表达时，观察到了更强的生长抑制作用。PER 2对乳腺癌细胞的抑制作用还通过其对MCF-7细胞非锚定依赖性生长的抑制得以证明，这表现为集落数量和大小的减少。单独表达PER 2或与CRY 2共同表达时，还观察到MCF-7细胞在细胞周期的G1期相应受阻。PER 2的表达还诱导了MCF-7乳腺癌细胞的凋亡，这通过聚（ADP-核糖）聚合酶（PARP）裂解增加得以证明。最后，我们的研究表明，MCF-7乳腺癌细胞中PER 2的表达与细胞周期蛋白D1表达的显著降低和p53水平的上调有关。
