Demethylation of MAGE promoters during gastric cancer progression.
Demethylation of MAGE promoters during gastric cancer progression.
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DOI：
10.1038/sj.bjc.6601600
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发表时间：
2004-02-23
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
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黑色素瘤抗原（法师）编码基因通过其启动子CpG岛的去甲基化在各种肿瘤类型中表达，所述启动子CpG岛在除睾丸和胎盘之外的所有非肿瘤组织中是沉默的。胃癌中法师基因去甲基化的临床病理意义尚不清楚。我们通过甲基化特异性PCR（MSP）研究了10种胃癌细胞系和84例胃癌患者手术标本中MAGE-A1和-A3启动子甲基化状态。RT-PCR检测MAGE-A1和MAGE-A3在10株胃癌细胞系中的表达。然后评估法师启动子甲基化状态与胃癌患者临床病理特征之间的任何相关性。10个胃癌细胞系中有8个显示MAGE-A1和-A3的去甲基化，其余两个细胞系显示MAGE-A1或-A3的去甲基化。MAGE-A1和MAGE-A3分别在10个胃癌细胞系中的7个和9个中表达。MAGE-A1和MAGE-A3启动子分别在29%（25/84）和66%（56/84）的胃肿瘤标本中发生去甲基化。MAGE-A1和MAGE-A3启动子的去甲基化（n=22）在晚期胃癌患者中更常见（P=0.0035），与未去甲基化的患者（n=25）相比，这些患者也表现出更高的淋巴结转移发生率（P=0.0007）。此外，去甲基化患者的预后往往更差，尽管这种差异没有统计学意义（P=0.183）。MAGE-A1和MAGE-A3的去甲基化发生在胃癌的进展阶段，并且可能与胃癌的侵袭性生物学行为相关。
Melanoma antigen (MAGE)-encoding genes are expressed in various tumour types via demethylation of their promoter CpG islands, which are silent in all non-neoplastic tissues except for the testis and placenta. The clinicopathological significance of demethylation of MAGE genes in gastric carcinoma is not known. We investigated the promoter methylation status of MAGE-A1 and -A3 in 10 gastric cancer cell lines and in surgical specimens from 84 gastric cancer patients by methylation-specific PCR (MSP). Expression of MAGE-A1 and -A3 in the 10 gastric cancer cell lines was also investigated by RT–PCR. Any correlation between the methylation status of the MAGE promoters and clinicopathological characteristics of the gastric cancer patients was then assessed. Eight of the 10 gastric cancer cell lines showed demethylation of both MAGE-A1 and -A3, and the remaining two cell lines did either of MAGE-A1 or -A3. Expression of MAGE-A1 and -A3 was confirmed in seven and nine of the 10 gastric cancer cell lines, respectively. The MAGE-A1 and -A3 promoters were demethylated in 29% (25 out of 84) and 66% (56 out of 84) of the gastric tumour specimens, respectively. Demethylation of both MAGE-A1 and -A3 promoters (n=22) was found more frequently in gastric cancer patients in advanced clinical stages (P=0.0035), and these patients also exhibited a higher incidence of lymph node metastasis (P=0.0007) compared to those patients without demethylation (n=25). Furthermore, demethylation patients tended to have a worse prognosis, although this difference was not statistically significant (P=0.183). Demethylation of MAGE-A1 and -A3 occurs during progressive stages of gastric cancer, and may be associated with aggressive biological behaviour of gastric cancer.
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DOI：
10.1111/j.1349-7006.2001.tb02153.x
发表时间：
2001-12
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Choi JH;Kwon HJ;Yoon BI;Kim JH;Han SU;Joo HJ;Kim DY
通讯作者：
Kim DY
影响因子：
56.9
作者：
Gaudet, F;Hodgson, JG;Jaenisch, R
通讯作者：
Jaenisch, R
影响因子：
3.2
作者：
DEPLAEN, E;ARDEN, K;BOON, T
通讯作者：
BOON, T
影响因子：
56.9
作者：
GOELZ, SE;VOGELSTEIN, B;FEINBERG, AP
通讯作者：
FEINBERG, AP
影响因子：
2.6
作者：
Kim, JH;Shioya, M;Nakatani, M
通讯作者：
Nakatani, M