美國耶希瓦大學(xué)5月12日報告說,，該校愛因斯坦醫(yī)學(xué)院研究人員最新研究發(fā)現(xiàn),，發(fā)生轉(zhuǎn)移的乳腺癌細胞中，一種名為ZBP1的基因處于“沉默”狀態(tài),。
研究負責(zé)人羅伯特·辛格說,，通過檢測這一基因，有助于醫(yī)生判斷乳腺癌是否開始轉(zhuǎn)移,，甚至有望開發(fā)出阻止癌細胞轉(zhuǎn)移的新藥,。
辛格等人幾年前就在研究中發(fā)現(xiàn)，ZBP1基因在細胞的移動,、發(fā)育,、空間分布中發(fā)揮重要作用。他們當時觀察發(fā)現(xiàn),，這一基因在胚胎發(fā)育過程中異?；钴S，但在成年人體內(nèi)基本上處于“沉默”狀態(tài),。
后來的研究卻發(fā)現(xiàn),，ZBP1基因在包括乳腺癌在內(nèi)的幾種癌細胞中會被重新激活。不過,，在發(fā)生轉(zhuǎn)移的癌細胞中,，該基因卻又重新“沉默”。
辛格領(lǐng)導(dǎo)的研究小組在新一期《細胞科學(xué)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(jié)果發(fā)現(xiàn),，當有甲基附著到ZBP1的“基因啟動區(qū)域（即基因中啟動基因表達的片段）”時,，這個類似基因“發(fā)動機”的區(qū)域由于“甲基化”就無法與一種特殊蛋白質(zhì)結(jié)合，導(dǎo)致基因無法表達,，被迫“沉默”,。
研究還發(fā)現(xiàn)，ZBP1基因“沉默”后,，癌細胞的移動能力增強,，而且會促進轉(zhuǎn)移后的癌細胞增殖。
這一成果對于預(yù)測乳腺癌轉(zhuǎn)移非常重要,。研究小組說,，當ZBP1基因出現(xiàn)“沉默”跡象時，就表明癌細胞可能要轉(zhuǎn)移,，預(yù)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(zhì)結(jié)合,，可能會降低癌細胞轉(zhuǎn)移的能力。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
