DNA hypermethylation of TIMP3 gene in invasive breast ductal carcinoma
DNA hypermethylation of TIMP3 gene in invasive breast ductal carcinoma
复制标题
DOI：
10.1016/s0753-3322(05)80079-4
复制
发表时间：
2005-10-01
影响因子：
7.5
通讯作者：
Chow, LWC
中科院分区：
文献类型：
--
作者：
Lui, ELH;Loo, WTY;Chow, LWC
背景。-肿瘤细胞通常显示异常甲基化和多个基因的沉默，包括调节关键过程如细胞周期控制、DNA修复和血管生成的肿瘤抑制基因（TSG）。金属蛋白酶组织抑制剂3（TIMP 3）是一种细胞外基质结合蛋白，调节基质组成，影响肿瘤生长、侵袭和血管生成。它通过阻断VEGF与VEGF受体-2的结合来介导血管内皮生长因子（VEGF），并抑制下游信号传导。本研究集中于浸润性乳腺导管癌（IDC）样本中TIMP 3基因的高甲基化状态与临床参数。对173例浸润性乳腺癌患者进行DNA提取和甲基化特异性PCR（MSP）检测。每个基因的特异性甲基化和未甲基化引物都用于PCR，产物在琼脂糖凝胶上可视化。然后将TIMP 3的甲基化状态与相应患者的临床病理特征进行比较。乳腺癌组织中TIMP 3基因甲基化频率为20.81%。高甲基化癌中Ⅱ ~ Ⅲ级占50%，淋巴结转移（LN）阳性率为44.44%，淋巴管浸润（LVP）阳性率为36.11%，雌激素受体（ER）、孕激素受体（PR）和c-erbB 2过度表达分别为44.44%、22.22%和47.22%。提示TIMP 3基因甲基化可能与IDC的高分级和淋巴结转移有关。ER、PR和c-erbB 2的过度表达。(c)2005年，Elsevier SAS。All rights reserved.
Background.-Neoplastic cells often display aberrant methylation and silencing of multiple genes, including tumor suppressor genes (TSGs) that regulate critical processes such as cell cycle control, DNA repair and angiogenesis. Tissue inhibitor of metalloprotemase-3 (TIMP3) is an extracellular matrix-bound protein which regulates matrix composition and affects tumor growth, invasion and angiogenesis. It mediates vascular endothelial growth factor (VEGF) by blocking the binding of VEGF to VEGF receptor-2 and inhibits downstream signaling. This study focused on the hypermethylation status of the TIMP3 gene with clinical parameters in invasive breast ductal carcinoma (IDC) samples.Materials and methods.-DNA extraction and methylation specific PCR (MSP) was performed on 173 patients with invasive breast carcinoma. Both specific methylated and unmethylated primers for each gene were used for PCR and the products were visualized on agarose gel. The methylation status of TIMP3 was then compared with corresponding patients' clinicopathologic characteristics.Results.-Methylation frequencies of TIMP3 in the breast cancer samples were 20.81%. Among the hypermethylated cancers, 50% were tumor grade II-III, 44.44% were positive in lymph node involvement (LN), 36.11% were positive in lymphovascular permeation (LVP); 44.44%, 22.22% and 47.22% for the overexpressions in estrogen receptor (ER), progesterone receptor(PR) and c-erbB2, respectively.Conclusion.-The result demonstrated that hypermethylation of TIMP3 in IDC might be associated with high tumor grading and lymph nodes metastasis. and overexpression of ER, PR and c-erbB2, respectively. (c) 2005 Elsevier SAS. All rights reserved.