美國(guó)密歇根大學(xué)的一個(gè)研究小組發(fā)現(xiàn)，腦癌與大腦神經(jīng)干細(xì)胞中的腫瘤抑制基因p53缺陷有關(guān),。此項(xiàng)發(fā)現(xiàn)將有助于找到更好的預(yù)防和治療腦癌的方法。該研究成果刊發(fā)在6月2日出版的《癌細(xì)胞》雜志上,。
研究文章稱,，研究人員首次發(fā)現(xiàn)，惡性膠質(zhì)瘤可能源于位于在腦下室區(qū)（SVZ）的神經(jīng)干細(xì)胞,；在試驗(yàn)小鼠身上,，神經(jīng)干細(xì)胞巢內(nèi)的干細(xì)胞會(huì)制造很多具有專門用途的神經(jīng)細(xì)胞并釋放出去。而腫瘤抑制基因p53的突變使得神經(jīng)干細(xì)胞和它制造的神經(jīng)細(xì)胞一樣出現(xiàn)轉(zhuǎn)移,，從而誘發(fā)腦瘤。
惡性膠質(zhì)瘤,，也稱為多形性膠質(zhì)母細(xì)胞瘤,，是一種非常難以治療的癌癥。目前幾乎所有的治療方法,，包括手術(shù),、放療和化療，都不太有效,，其死亡率在20多年來(lái)一直未有改觀,。科學(xué)家最近發(fā)現(xiàn),，某些基因和細(xì)胞的作用途徑在惡性膠質(zhì)瘤中被改變,，其中最關(guān)鍵的變化就包括p53基因突變。但科學(xué)家一直不知道是什么類型細(xì)胞的p53缺陷促成腦細(xì)胞發(fā)生癌變,。
密歇根大學(xué)醫(yī)學(xué)院的副教授朱原（音譯）博士帶領(lǐng)的研究小組采用中樞神經(jīng)系統(tǒng)具有p53變異的小鼠進(jìn)行了一系列試驗(yàn),。他們發(fā)現(xiàn)，這些小鼠中大多數(shù)得了惡性腦腫瘤,，腫瘤細(xì)胞中都出現(xiàn)了p53變異,。該發(fā)現(xiàn)將有助于對(duì)惡性膠質(zhì)瘤進(jìn)行及時(shí)有效的早期篩查，表明變異p53可作為一個(gè)有用的標(biāo)記,，在各種階段跟蹤神經(jīng)膠質(zhì)瘤細(xì)胞,。而在發(fā)病早期檢測(cè)到疾病，無(wú)疑會(huì)提高治療的成功幾率,。這個(gè)發(fā)現(xiàn)也會(huì)有助于改善治療手段,，降低此種癌癥患者的死亡率。如果人類的惡性膠質(zhì)瘤同小鼠一樣源于腦下室區(qū)的神經(jīng)干細(xì)胞,，就必須在早期的診斷和治療階段更多地關(guān)注干細(xì)胞巢,，如同對(duì)待腫瘤一樣對(duì)待它，進(jìn)行有針對(duì)性的直接治療,，以消除癌癥源并防止它死灰復(fù)燃,。
研究結(jié)果表明,，老鼠大腦的神經(jīng)干細(xì)胞具有較高的積累遺傳病變的潛力，并成為癌細(xì)胞的攻擊標(biāo)靶,。從某種程度上講,，癌癥細(xì)胞在早期階段與正常的干細(xì)胞并沒有太大的差別，但它非正常地結(jié)合了神經(jīng)干細(xì)胞（自我更新）和專業(yè)子代（轉(zhuǎn)移）的關(guān)鍵特征,。在能夠?qū)ζ溥M(jìn)行約束以治療疾病之前,，必須要對(duì)其有更廣泛深入的了解。朱原小組發(fā)現(xiàn)這些有p53突變的細(xì)胞具有高度適應(yīng)性,，如果治療阻止了它們的活動(dòng)路徑,，它們則會(huì)學(xué)著找到另一種方式來(lái)成長(zhǎng)，這解釋了為什么惡性膠質(zhì)瘤會(huì)產(chǎn)生抗藥性,。
朱原小組計(jì)劃繼續(xù)進(jìn)行小鼠實(shí)驗(yàn),，看看p53的功能是否可以在腫瘤細(xì)胞中恢復(fù)。他們也要檢驗(yàn)抑制腦下室區(qū)的神經(jīng)干細(xì)胞是否會(huì)是一種潛在的治療手段,。（生物谷Bioon.com）
生物谷推薦原始出處：
Cancer Cell, 2 June 2009 doi:10.1016/j.ccr.2009.04.001
Expression of Mutant p53 Proteins Implicates a Lineage Relationship between Neural Stem Cells and Malignant Astrocytic Glioma in a Murine Model
Yuan Wang1,2,6,Jiong Yang1,2,6,Huarui Zheng1,2,Gerald J. Tomasek1,2,Peng Zhang1,2,Paul E. McKeever3,Eva Y.-H.P. Lee4,5andYuan Zhu1,2,,
1 Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA
2 Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
3 Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
4 Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA
5 Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA
6 These authors contributed equally to this work
Recent studies have identified genes and core pathways that are altered in human glioblastoma. However, the mechanisms by which alterations of these glioblastoma genes singly and cooperatively transform brain cells remain poorly understood. Further, the cell of origin of glioblastoma is largely elusive. By targeting a p53 in-frame deletion mutation to the brain, we show that p53 deficiency provides no significant growth advantage to adult brain cells, but appears to induce pleiotropic accumulation of cooperative oncogenic alterations driving gliomagenesis. Our data show that accumulation of a detectable level of mutant p53 proteins occurs first in neural stem cells in the subventricular zone (SVZ) and that subsequent expansion of mutant p53-expressing Olig2+ transit-amplifying progenitor-like cells in the SVZ-associated areas initiates glioma formation.
