Cytoplasmic RASSF2A is a proapoptotic mediator whose expression is epigenetically silenced in gastric cancer

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

COLLETOTRICHUM ACUTATUM ニ ヨル ハナミズキタンソビョウ

2004年6月,東京都世田谷区の街路樹に植栽されていたハナミズキ(Cornus florida L.)の葉に,淡褐色,不整形の病斑を生じ,その上に炭疽病菌と思われる分生子粘塊が観察される病害が発生した。病斑は,はじめ葉の周縁部および中央部が褐色となり,それぞれ不定形に拡大,融合し,その後,葉の全体が褐変後,早期に落葉した。病斑部の分生子層には,無色,単胞,紡錘形で,大きさ11～14×3.1～4.2μm(平均13.4×3.8μm)の分生子が形成されていた。分生子は発芽時に褐色,厚膜,棍棒状,大きさ7.7～11.5×5.1～7.7μm(平均8.8×5.6μm)の付着器を形成した。また,分離菌を健全なハナミズキに接種した結果,自然発生と同様な病徴が再現された。これらの結果から,本病はColletotrichum acutatum Simmonds ex Simmondsによって引き起こされる病害であることが確認された。本菌によるハナミズキの病害はわが国では未報告であることから,本病をハナミズキ炭疽病と呼称することを提案した。In June 2004, diseased leaves with lesions characterized as anthracnose were found on Flowering Dogwood (Cornus florida L.) planted on a roadside in Setagaya, Tokyo, Japan. These lesions were light-brown to brown in color with yellowish margin and irregular-shaped. Globose and salmon pinkish acervuli were formed on their surface. Conidia are aseptate, hyaline, fusiform or ellipsoid with pointed ends, and measured 11～14×3.1～4.2μm (13.4×3.8μm in average). Appressoria are ellipsoid to obovate with smooth margins and brown colored, 7.7～11.5×5.1～7.7μm (8.8×5.6μm in average). The causal fungus was identified as Colletotrichum acutatum Simmonds ex Simmonds. The pathogenicity was confirmed by the artificial inoculation test. This is the first report describing the Flowering Dogwood disease caused by C. acutatum in Japan. Anthracnose of Flowering Dogwood was proposed as a new disease in Japan