DSC3 expression is regulated by p53, and methylation of DSC3 DNA is a prognostic marker in human colorectal cancer.
DSC3 expression is regulated by p53, and methylation of DSC3 DNA is a prognostic marker in human colorectal cancer.
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DOI：
10.1038/bjc.2011.28
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发表时间：
2011-03-15
影响因子：
8.8
通讯作者：
Petersen I
中科院分区：
文献类型：
--
作者：
Cui T;Chen Y;Yang L;Knösel T;Zöller K;Huber O;Petersen I
桥粒胶蛋白3（DSC3）是钙粘蛋白超家族的成员，是桥粒的组成部分，参与肿瘤的发生。然而，DSC3在结直肠癌（CRC）中的作用尚未确定。通过RT-PCR和蛋白质印迹分析结索胶蛋白3在CRC细胞系中的表达。通过去甲基化试验、甲基化特异性PCR和亚硫酸氢盐测序（BS）检查DSC3的甲基化状态。通过转染研究p53的调节作用。结索胶蛋白3在结直肠癌细胞中在mRNA和蛋白水平下调。5-氮-2 ′-脱氧胞苷（DAC）处理后，7个细胞系中有5个恢复了桥粒胶原3的表达。BS法检测到DSC3基因启动子区和外显子1的甲基化模式不均一。在41%（41/99）的原发性CRC中发现了DSC3基因组序列甲基化，与不良预后相关（P = 0.002）。单独转染p53或与DAC联合转染均可增加DSC3的表达。类似地，用p53诱导剂阿霉素单独或与DAC组合处理增强DSC3表达。DNA甲基化有助于CRC细胞系中DSC3的下调。DSC3 DNA的甲基化状态是CRC的预后标志物。P53似乎在调节DSC3表达中具有重要作用。
Desmocollin 3 (DSC3), a member of the cadherin superfamily and integral component of desmosomes, is involved in carcinogenesis. However, the role of DSC3 in colorectal cancer (CRC) has not yet been established. Desmocollin 3 expression in CRC cell lines was analysed by RT–PCR and western blotting. Methylation status of DSC3 was examined by demethylation tests, methylation-specific PCR, and bisulphite sequencing (BS). The regulatory role of p53 was investigated by transfection. Desmocollin 3 was downregulated in CRC cells at mRNA and protein levels. Desmocollin 3 expression was restored in five out of seven cell lines after 5-aza-2′-deoxycytidine (DAC) treatment. A heterogeneous methylation pattern was detected by BS in promoter region and exon 1 of DSC3. Methylation of DSC3 genomic sequences was found in 41% (41 out of 99) of primary CRC, being associated with poor prognosis (P=0.002). Transfection of p53 alone or in combination of DAC increased the DSC3 expression. Similarly, treatment with p53 inducer adriamycin alone or in combination with DAC enhanced DSC3 expression. DNA methylation contributes to downregulation of DSC3 in CRC cell lines. Methylation status of DSC3 DNA is a prognostic marker for CRC. P53 appears to have an important role in regulating DSC3 expression.
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DOI：
10.1186/bcr1273
发表时间：
2005
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Oshiro MM;Kim CJ;Wozniak RJ;Junk DJ;Muñoz-Rodríguez JL;Burr JA;Fitzgerald M;Pawar SC;Cress AE;Domann FE;Futscher BW
通讯作者：
Futscher BW
影响因子：
8
作者：
Adachi, K;Toyota, M;Tokino, T
通讯作者：
Tokino, T
影响因子：
168.9
作者：
Cunningham, David;Atkin, Wendy;Starling, Naureen
通讯作者：
Starling, Naureen
影响因子：
8
作者：
Chen, Y-J;Chang, J. T.;Cheng, A-J
通讯作者：
Cheng, A-J
影响因子：
64.8
作者：
BUCKBINDER, L;TALBOTT, R;KLEY, N
通讯作者：
KLEY, N