一項(xiàng)新的研究關(guān)于干細(xì)胞生長(zhǎng)和分化關(guān)鍵步驟的發(fā)生，以及該步驟的逆轉(zhuǎn)導(dǎo)致癌癥的機(jī)制,。研究人員表示，有3個(gè)主要的蛋白，它們首先會(huì)激活干細(xì)胞增殖,，然后隨著細(xì)胞分化成最終的類型，這些蛋白會(huì)改變功能,，使得細(xì)胞不在分裂,。因此這些蛋白或能為許多癌癥提供一個(gè)安全新穎的治療靶標(biāo)。
在正在發(fā)育的動(dòng)物中,，干細(xì)胞會(huì)增殖和分化形成生命所需要的器官,。這項(xiàng)新的研究表明，在這個(gè)過程中,，某一關(guān)鍵的步驟的發(fā)生,，以及該過程的逆轉(zhuǎn)導(dǎo)致癌癥的機(jī)制。
研究人員表示,，有三種蛋白在干細(xì)胞轉(zhuǎn)變成最終類型過程中承擔(dān)了重要的角色,。這三種蛋白分別叫E2f1,E2f2和E2f3。
這些蛋白能夠刺激干細(xì)胞生長(zhǎng)和分化,。但是一旦干細(xì)胞開始分化成最終的細(xì)胞類型-比如視網(wǎng)膜細(xì)胞或腸細(xì)胞,，這3種蛋白會(huì)轉(zhuǎn)變功能使干細(xì)胞不再分裂。這項(xiàng)研究同樣描述了這些蛋白如何在眼癌基因（retinoblastoma,，Rb）突變的細(xì)胞中再次轉(zhuǎn)變功能,。Rb基因變異存在于在許多的癌癥中，這表明,，這些蛋白可能提供一個(gè)安全新穎的治療靶標(biāo)定位這些腫瘤,。
這項(xiàng)研究結(jié)果發(fā)布在12月17日的Nature上。研究人員表示,，這些E2fs是干細(xì)胞的基因激活因子,，但另一方面當(dāng)干細(xì)胞開始分化時(shí)它們會(huì)轉(zhuǎn)變成基因抑制因子。
這是細(xì)胞分化過程中很重要的一步,。在器官形成過程中,，由于只需要固定數(shù)量的細(xì)胞，所以需要在分化的過程中進(jìn)行抑制。蛋白質(zhì)這種從激活因子到抑制因子的改變是停止細(xì)胞繼續(xù)增殖必需的,。在這之前,，科學(xué)家認(rèn)為，這些蛋白對(duì)分化的細(xì)胞具有重要作用,，但只是在增殖的細(xì)胞中起作用,，比如干細(xì)胞，其實(shí)這是不正確的,。
如果我們可以抑制癌細(xì)胞中的這些蛋白,，或許就能預(yù)防腫瘤生長(zhǎng)，而且不會(huì)對(duì)正常細(xì)胞產(chǎn)生很大的影響,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 462, 930-934 (17 December 2009) | doi:10.1038/nature08677
E2f1–3 switch from activators in progenitor cells to repressors in differentiating cells
Jean-Leon Chong1,2,3,9, Pamela L. Wenzel1,2,3,9,10, M. Teresa Sáenz-Robles4,9, Vivek Nair1,2,3, Antoney Ferrey1,2,3, John P. Hagan1,3, Yorman M. Gomez1,2,3, Nidhi Sharma1,2,3, Hui-Zi Chen1,2,3, Madhu Ouseph1,2,3, Shu-Huei Wang1,2,3, Prashant Trikha1,2,3, Brian Culp1,2,3, Louise Mezache1,2,3, Douglas J. Winton5, Owen J. Sansom6, Danian Chen7, Rod Bremner7, Paul G. Cantalupo4, Michael L. Robinson8, James M. Pipas4 & Gustavo Leone1,2,3
1 Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine,
2 Department of Molecular Genetics, College of Biological Sciences,
3 Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA
4 Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
5 Cambridge Research Institute, Li Ka Shing Centre, Cambridge CB2 0RE, UK
6 The Beatson Institute for Cancer Research, Glasgow G61 1BD, UK
7 Toronto Western Research Institute, University Health Network, Departments of Ophthalmology and Visual Science, and Laboratory Medicine and Pathobiology, University of Toronto, Ontario M5T 2S8, Canada
8 Department of Zoology, Miami University, Oxford, Ohio 45056, USA
9 These authors contributed equally to this work.
10 Present address: Division of Pediatric Hematology/Oncology, Children’s Hospital Boston; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
11 Correspondence to: Gustavo Leone1,2,3 Correspondence and requests for materials should be addressed to G.L.
In the established model of mammalian cell cycle control, the retinoblastoma protein (Rb) functions to restrict cells from entering S phase by binding and sequestering E2f activators (E2f1, E2f2 and E2f3), which are invariably portrayed as the ultimate effectors of a transcriptional program that commit cells to enter and progress through S phase1, 2. Using a panel of tissue-specific cre-transgenic mice and conditional E2f alleles we examined the effects of E2f1, E2f2 and E2f3 triple deficiency in murine embryonic stem cells, embryos and small intestines. We show that in normal dividing progenitor cells E2f1–3 function as transcriptional activators, but contrary to the current view, are dispensable for cell division and instead are necessary for cell survival. In differentiating cells E2f1–3 function in a complex with Rb as repressors to silence E2f targets and facilitate exit from the cell cycle. The inactivation of Rb in differentiating cells resulted in a switch of E2f1–3 from repressors to activators, leading to the superactivation of E2f responsive targets and ectopic cell divisions. Loss of E2f1–3 completely suppressed these phenotypes caused by Rb deficiency. This work contextualizes the activator versus repressor functions of E2f1–3 in vivo, revealing distinct roles in dividing versus differentiating cells and in normal versus cancer-like cell cycles.
