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美國耶希瓦大學5月12日報告說，該校愛因斯坦醫學院研究人員最新研究發現，發生轉移的乳腺癌細胞中，一種名為ZBP1的基因處于“沉默”狀態。 研究負責人羅伯特·辛格說，通過檢測這一基因，有助于醫生判斷乳腺癌是否開始轉移，甚至有望開發出阻止癌細胞轉移的新藥。 辛格等人幾年前就在研究中發現，ZBP1基因在細胞的移動、發育、空間分布中發揮重要作用。他們當時觀察發現，這一基因在胚胎發育過程中異常活躍，但在成年人體內基本上處于“沉默”狀態。 后來的研究卻發現，ZBP1基因在包括乳腺癌在內的幾種癌細胞中會被重新激活。不過，在發生轉移的癌細胞中，該基因卻又重新“沉默”。 辛格領導的研究小組在新一期《細胞科學雜志》（Journal of Cell Science）上介紹說，在最新的實驗中，他們對小鼠、大鼠和人類的乳腺癌細胞中ZBP1基因的作用機制進行了深入研究。 結果發現，當有甲基附著到ZBP1的“基因啟動區域（即基因中啟動基因表達的片段）”時，這個類似基因“發動機”的區域由于“甲基化”就無法與一種特殊蛋白質結合，導致基因無法表達，被迫“沉默”。 研究還發現，ZBP1基因“沉默”后，癌細胞的移動能力增強，而且會促進轉移后的癌細胞增殖。 這一成果對于預測乳腺癌轉移非常重要。研究小組說，當ZBP1基因出現“沉默”跡象時，就表明癌細胞可能要轉移，預知這一點將有助于選擇適宜的治療方案。另外，假如能夠借助某種化合物，使得ZBP1基因與上述特殊蛋白質結合，可能會降低癌細胞轉移的能力。 推薦原始出處： Journal of Cell Science 122, 1584-1594 (2009) Endocytosis of MHC molecules by distinct membrane rafts Ruth Knorr, Claudia Karacsonyi and Robert Lindner* Department of Cell Biology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany In B-lymphocytes, endocytosis of MHC I and MHC II molecules is important for the cross-priming and presentation of labile antigens, respectively. Here, we report that MHC I and MHC II were internalized by separate endocytic carriers that lacked transferrin receptor. Cholera toxin B was co-internalized with MHC II, but not with MHC I, suggesting that the CLIC/GEEC pathway is involved in the uptake of MHC II. Endocytosis of MHC I and MHC II was inhibited by filipin, but only MHC II showed a strong preference for a membrane raft environment in a co-clustering analysis with GM1. By using a novel method for the extraction of detergent-resistant membranes (DRMs), we observed that MHC I and MHC II associate with two distinct types of DRMs. These differ in density, protein content, lipid composition, and ultrastructure. The results of cell surface biotinylation and subsequent DRM isolation show that precursors for both DRMs coexist in the plasma membrane. Moreover, clustering of MHC proteins at the cell surface resulted in shifts of the respective DRMs, revealing proximity-induced changes in the membrane environment. Our results suggest that the preference of MHC I and MHC II for distinct membrane rafts directs them to different cellular entry points. (責任編輯：Doctor001) |
