Period-2: a tumor suppressor gene in breast cancer.
Period-2: a tumor suppressor gene in breast cancer.
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DOI：
10.1186/1740-3391-6-4
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发表时间：
2008-03-11
影响因子：
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通讯作者：
Hill, Steven M
中科院分区：
文献类型：
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作者：
Xiang, Shulin;Coffelt, Seth B;Mao, Lulu;Yuan, Lin;Cheng, Qi;Hill, Steven M
以前的报道表明，Period 2基因(PER 2)的消融会促进小鼠淋巴瘤和白血病的发展。通过免疫印迹分析，我们已经证明了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，当PER-2与Cry-2基因共表达时，对MCF-7细胞的生长抑制作用更强。PER-2对乳腺癌细胞的抑制作用也表现为抑制MCF-7细胞的非贴壁生长，表现为克隆数量和大小的减少。单独表达PER-2或与CRY-2联合作用时，MCF-7细胞也被阻滞在细胞周期的G1期。PER-2的表达也诱导了MCF-7乳腺癌细胞的凋亡，表现为PARP[聚(ADP-核糖)聚合酶]裂解增加。最后，我们的研究表明，在MCF-7乳腺癌细胞中，PER-2的表达与细胞周期蛋白D1的表达显著降低和P53水平的上调有关。
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.