Methyl-CpG-DNA binding proteins in human prostate cancer: expression of CXXC sequence containing MBD1 and repression of MBD2 and MeCP2
Methyl-CpG-DNA binding proteins in human prostate cancer: expression of CXXC sequence containing MBD1 and repression of MBD2 and MeCP2
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DOI：
10.1016/s0006-291x(03)00253-5
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发表时间：
2003-03-21
影响因子：
3.1
通讯作者：
Dahiya, R
中科院分区：
文献类型：
--
作者：
Patra, SK;Patra, A;Dahiya, R
我们分析了前列腺癌细胞系、良性前列腺上皮（BPH-1）细胞系、49个BPH组织和46个前列腺癌组织中MBD 1、MBD 2、MBD 3、MBD 4和MeCP 2的基因表达和MBD 1、MBD 2和MeCP 2的蛋白表达。本研究的结果表明，MBD 2基因在所有样品中表达，MeCP 2基因在所有癌细胞系中表达，但在BPH-1细胞系中不表达。然而，在癌细胞系和癌组织中没有MBD 2和MeCP 2的蛋白表达。对于含有MBD 1的CXXC序列，蛋白质和mRNA在癌细胞系、癌组织、BPH-1细胞系和BPH组织中均表达。我们注意到，在。在BPH组织和低度恶性肿瘤组织中，MBD I蛋白的表达非常高，随着恶性程度的增加，表达逐渐降低。用蛋白酶体抑制剂（MG-132）处理癌细胞系不能恢复MBD 2和MeCP 2蛋白的表达。当前列腺癌细胞系用低甲基化剂、5-氮杂-2 '-脱氧胞苷（DNMT抑制剂）处理时，HDAC 1和HDAC 2表达降低。这是第一个报告表明，CXXC序列包含MBD 1过表达，可以是主要因素的高甲基化染色质片段通过HDAC 1/2易位和组蛋白去乙酰化在人前列腺癌。(C)2003 Elsevier Science（美国）。All rights reserved.
We analyzed gene expression of MBD1, MBD2, MBD3, MBD4, and MeCP2 and protein expression of MBD1, MBD2, and MeCP2 in prostate cancer cell lines, benign prostate epithelium (BPH-1) cell line, 49 BPH tissues, and 46 prostate cancer tissues. The results of this study demonstrate that MBD2 gene is expressed in all samples and MeCP2 gene is expressed in all cancer cell lines but not in BPH-1 cell line. However, there was no protein expression for MBD2 and MeCP2 in cancer cell lines and cancer tissues. For CXXC sequence containing MBD 1, both protein and mRNA were expressed in cancer cell lines, cancer tissues, BPH-1 cell line, and BPH tissues. We observed that, in. BPH tissues and low-grade cancer tissues, MBD I protein expression was very high and gradually decreased with increase of cancer grade. Treatment of cancer cell lines with proteasome inhibitor (MG-132) did not restore expression of MBD2 and MeCP2 proteins. When prostate cancer cell lines were treated with hypontethylating agent, 5-aza-2'-deoxycytidine (DNMT inhibitor), HDAC I and HDAC2 expression was decreased. This is the first report demonstrating that CXXC sequence containing MBD1 is overexpressed and can be the major factor of hypermethylated chromatin segments through HDAC1/2 translocation and histone deacetylation in human prostate cancer. (C) 2003 Elsevier Science (USA). All rights reserved.