Winter Sherry L, Bosnoyan-Collins Lucine, Pinnaduwage Dushanthi, Andrulis Irene L
Fred A. Litwin Center for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Neoplasia. 2007 Oct;9(10):797-800. doi: 10.1593/neo.07595.
There is a growing body of evidence implicating aberrant circadian clock expression in the development of cancer. Based on our initial experiments identifying a putative interaction between BRCA1 and the clock proteins Per1 and Per2, as well as the reported involvement of the circadian clock in the development of cancer, we have performed an expression analysis of the circadian clock genes Per1 and Per2 in both sporadic and familial primary breast tumors and normal breast tissues using real-time polymerase chain reaction. Significantly decreased levels of Per1 were observed between sporadic tumors and normal samples (P < .00001), as well as a further significant decrease between familial and sporadic breast tumors for both Per1 (P < .00001) and Per2 (P < .00001). Decreased Per1 was also associated with estrogen receptor negativity (53% vs 15%, P = .04). These results suggest a role for both Per1 and Per2 in normal breast function and show for the first time that deregulation of the circadian clock may be an important factor in the development of familial breast cancer. Aberrant expression of circadian clock genes could have important consequences on the transactivation of downstream targets that control the cell cycle and on the ability of cells to undergo apoptosis, potentially promoting carcinogenesis.
越来越多的证据表明，昼夜节律时钟表达异常与癌症的发生发展有关。基于我们最初的实验，发现BRCA1与时钟蛋白Per1和Per2之间存在假定的相互作用，以及昼夜节律时钟与癌症发生发展的报道关联，我们使用实时聚合酶链反应对散发性和家族性原发性乳腺肿瘤及正常乳腺组织中的昼夜节律时钟基因Per1和Per2进行了表达分析。在散发性肿瘤与正常样本之间观察到Per1水平显著降低（P <.00001），并且在家族性和散发性乳腺肿瘤之间，Per1（P <.00001）和Per2（P <.00001）均进一步显著降低。Per1降低还与雌激素受体阴性相关（53%对15%，P =.04）。这些结果表明Per1和Per2在正常乳腺功能中发挥作用，并首次表明昼夜节律时钟失调可能是家族性乳腺癌发生发展的重要因素。昼夜节律时钟基因的异常表达可能对控制细胞周期的下游靶点的反式激活以及细胞发生凋亡的能力产生重要影响，从而潜在地促进癌变。
