Deregulated expression of the PER1, PER2 and PER3 genes in breast cancers
Deregulated expression of the PER1, PER2 and PER3 genes in breast cancers
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DOI：
10.1093/carcin/bgi075
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发表时间：
2005-07-01
期刊：
影响因子：
4.7
通讯作者：
Chang, JG
中科院分区：
文献类型：
--
作者：
Chen, ST;Choo, KB;Chang, JG
昼夜节律的破坏可能是乳腺癌发生的一个危险因素，但乳腺癌细胞中昼夜节律控制基因的分子变化仍然未被探索。我们使用免疫组织化学染色，甲基化特异性PCR和直接测序方法分析三个最重要的基因，即PER 1，PER 2和PER 3，在55例台湾妇女乳腺癌的昼夜节律的分子变化。我们的研究结果揭示了与附近的非癌细胞相比，在大多数（>95%）乳腺癌细胞中三个周期（PER）基因的表达的干扰。PER基因的失调不是由基因突变引起的，而很可能是由PER 1或PER 2启动子的甲基化引起的。PER基因启动子区甲基化与c-erbB 2表达有较强的相关性（P = 0.017）。由于生物钟控制着细胞周期相关基因的表达，我们认为PER基因表达的紊乱可能会导致正常生物钟控制的中断，从而有利于癌细胞的存活并促进癌的发生。昼夜节律基因在非癌细胞和癌细胞中的差异表达可能为乳腺癌的时间治疗提供分子基础。
Disruption of circadian rhythm may be a risk factor in the development of breast cancer, but molecular changes in circadian rhythm controlled genes in breast cancer cells are still unexplored. We used immunohistochemical staining, methylation specific PCR and direct sequencing methods to analyze molecular changes in three most important genes, namely PER1, PER2 and PER3, in circadian rhythm in 55 cases of breast cancer of Taiwanese women. Our results reveal disturbances in the expression of the three period (PER) genes in most (>95%) of the breast cancerous cells in comparison with the nearby non-cancerous cells. The PER gene deregulation is not caused by genetic mutations but most probably by methylation of the PER1 or PER2 promoter. Methylation of the PER gene promoters has a strong correlation with c-erbB2 expression (P = 0.017). Since the circadian clock controls expression of cell-cycle related genes, we suggest that disturbances in PER gene expression may result in disruption of the control of the normal circadian clock, thus benefiting the survival of cancer cells and promoting carcinogenesis. Differential expression of circadian genes in non-cancerous and cancerous cells may provide a molecular basis for chronotherapy of breast cancer.