Cytoplasmic RASSF2A is a proapoptotic mediator whose expression is epigenetically silenced in gastric cancer.
Cytoplasmic RASSF2A is a proapoptotic mediator whose expression is epigenetically silenced in gastric cancer.
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细胞质RASSF2A是一种促凋亡的介体，其表达在胃癌中表观遗传沉默。
DOI：
10.1093/carcin/bgn060
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发表时间：
2008-07
期刊：
影响因子：
4.7
通讯作者：
Tokino, Takashi
中科院分区：
文献类型：
--
作者：
Maruyama, Reo;Akino, Kimishige;Toyota, Minoru;Suzuki, Hiromu;Imai, Takashi;Ohe-Toyota, Mutsumi;Yamamoto, Eiichiro;Nojima, Masanori;Fujikane, Tomoko;Sasaki, Yasushi;Yamashita, Toshiharu;Watanabe, Yoshiyuki;Hiratsuka, Hiroyoshi;Hirata, Koichi;Itoh, Fumio;Imai, Kohzoh;Shinomura, Yasuhisa;Tokino, Takashi
胃癌细胞经常表现出Ras信号的改变，尽管其潜在的分子机制尚不完全清楚。我们检测了8个ras-association domain family （RASSF）基因和MST1/2的表达谱，发现RASSF2A在胃癌中最常下调。由于启动子甲基化，RASSF2A在10个胃癌细胞系中有6个完全沉默，用5-aza-2 ' -脱氧胞苷处理细胞后恢复表达。将RASSF2A引入非表达细胞系可抑制集落形成并诱导细胞凋亡。这些作用与RASSF2A的细胞质定位和细胞形态变化有关。互补DNA芯片分析显示，RASSF2A抑制炎症细胞因子的表达，这可能反过来抑制血管生成和侵袭。在原发性胃癌中，78例病例中有23例（29.5%）检测到RASSF2A异常甲基化，甲基化与无淋巴浸润、无静脉浸润、无淋巴结转移、不晚期、Epstein-Barr病毒、无p53突变和CpG岛甲基化存在高表型显著相关。这些结果表明，RASSF2A的表观遗传失活是胃癌亚群肿瘤发生所必需的。
Gastric cancer cells often show altered Ras signaling, though the underlying molecular mechanism is not fully understood. We examined the expression profile of eight ras-association domain family (RASSF) genes plus MST1/2 and found that RASSF2A is the most frequently downregulated in gastric cancer. RASSF2A was completely silenced in 6 of 10 gastric cancer cell lines as a result of promoter methylation, and expression was restored by treating the cells with 5-aza-2′-deoxycytidine. Introduction of RASSF2A into non-expressing cell lines suppressed colony formation and induced apoptosis. These effects were associated with the cytoplasmic localization of RASSF2A and morphological changes to the cells. Complementary DNA microarray analysis revealed that RASSF2A suppresses the expression of inflammatory cytokines, which may in turn suppress angiogenesis and invasion. In primary gastric cancers, aberrant methylation of RASSF2A was detected in 23 of 78 (29.5%) cases, and methylation correlated significantly with an absence of the lymphatic invasion, absence of venous invasion, absence of lymph node metastasis, less advanced stages, Epstein–Barr virus, absence of p53 mutations and the presence of the CpG island methylator phenotype-high. These results suggest that epigenetic inactivation of RASSF2A is required for tumorigenesis in a subset of gastric cancers.
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影响因子：
64.8
作者：
Rajagopalan, H;Bardelli, A;Velculescu, VE
通讯作者：
Velculescu, VE
影响因子：
5.7
作者：
Akino, Kimishige;Toyota, Minoru;Tokino, Takashi
通讯作者：
Tokino, Takashi
影响因子：
8
作者：
Allen, N. P. C.;Donninger, H.;Clark, G. J.
通讯作者：
Clark, G. J.
影响因子：
30.8
作者：
Dammann, R;Li, C;Pfeifer, GP
通讯作者：
Pfeifer, GP
影响因子：
6.2
作者：
Kusano, M;Toyota, M;Tokino, T
通讯作者：
Tokino, T