哺乳動物細胞有時會具有過多的染色體,,被稱作非整倍性(aneuploidy),這會對機體造成損害,通常會導(dǎo)致出生缺陷或死亡,不過幾乎總是非整倍性的腫瘤細胞似乎因此獲得了生長優(yōu)勢,。美國科學家近日研究稱,具有額外染色體的哺乳動物細胞擁有一些共同特征,,可被用來研發(fā)癌癥治療方法,。相關(guān)論文發(fā)表在10月31日的《科學》(Science)雜志上。
此次研究是首次在哺乳動物細胞中系統(tǒng)檢測非整倍性的作用,。美國麻省理工學院生物學教授Angelika Amon和同事研究了4種不同小鼠染色體的非整倍性,。研究人員發(fā)現(xiàn),,除了每個額外染色體具有特定的有害效應(yīng)之外,,非整倍性還在所有細胞中引起普遍反應(yīng)。
非整倍性細胞分裂速度非常緩慢,、體積巨大并顯示出其它的代謝變化,,表明這些細胞正處于壓力下,需要額外的能量來應(yīng)付由非整倍性導(dǎo)致的蛋白失衡,。
這一發(fā)現(xiàn)產(chǎn)生了一個矛盾——非整倍性表面看來賦予了細胞增殖劣勢,,但非整倍性腫瘤細胞卻能快速增殖。
對這一矛盾的解釋理論有多種,,其中一種是,,即使非整倍性細胞無法很好地生長,它們可能仍然比周圍的正常細胞長得好,。正如Amon所說,,“獨眼人是失明國度的國王。”
而Amon偏愛的理論是,,非整倍性向細胞施加了太多的壓力,,使得其比正常細胞產(chǎn)生了更多的突變,最終驅(qū)使它形成癌,。
不過,,還有可能的是,非整倍性在癌細胞的發(fā)育中并不起作用,,它只是腫瘤產(chǎn)生的副產(chǎn)品,。
Amon說:“現(xiàn)在我們可以尋找能特定地殺死非整倍性細胞的化合物,或那些一旦被敲除就將殺死非整倍性細胞的基因,。”而且,,Amon和同事已經(jīng)確定了一個有希望的候選者,。(生物谷Bioon.com)
生物谷推薦原始出處:
Science,Vol. 322. no. 5902, pp. 703 – 709,,Bret R. Williams,,Angelika Amon
Aneuploidy Affects Proliferation and Spontaneous Immortalization in Mammalian Cells
Bret R. Williams,1,2 Vineet R. Prabhu,1 Karen E. Hunter,1,2* Christina M. Glazier,1,2 Charles A. Whittaker,1 David E. Housman,1 Angelika Amon1,2
Aneuploidy, an incorrect number of chromosomes, is the leading cause of miscarriages and mental retardation in humans and is a hallmark of cancer. We examined the effects of aneuploidy on primary mouse cells by generating a series of cell lines that carry an extra copy of one of four mouse chromosomes. In all four trisomic lines, proliferation was impaired and metabolic properties were altered. Immortalization, the acquisition of the ability to proliferate indefinitely, was also affected by the presence of an additional copy of certain chromosomes. Our data indicate that aneuploidy decreases not only organismal but also cellular fitness and elicits traits that are shared between different aneuploid cells.
1 David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
2 Howard Hughes Medical Institute, MIT, E17-233, 40 Ames Street, Cambridge, MA 02139, USA.